bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of Flow Cytometry in the Diagnostic Evaluation of Recurrent or Persistent Nodular Lymphocyte-Predominant Hodgkin Lymphoma
Authors: Gisriel Savanah , Haberichter Kristle , Huang Sara , Huang James 
Published: September 2019

Abstract

Objectives
We previously reported that lymph nodes involved by nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) had unique flow cytometric features. To further validate their diagnostic utility, we have examined the flow cytometry features in cases of persistent lymphadenopathy (LAD) prior to the diagnosis of NLPHL or recurrent LAD following diagnosis and treatment for NLPHL.

Methods
We retrospectively identified nine patients (2-3 specimens per patient for a total of 20 specimens) with persistent or recurrent lymphadenopathy before or after they were diagnosed with NLPHL between the ages of 13 and 76 years. Their histopathology diagnoses were reviewed and flow cytometry data were reanalyzed.

Results
Based on our published criteria (Am J Clin Pathol 2016;145:107-115), positive flow cytometry findings (at least 12% of T cells expressing CD57 or at least 3% of T cells coexpressing CD4 and CD8) were seen in 18 specimens. Based on histopathology, 11 of them were correctly diagnosed as NLPHL, 3 of them initially underdiagnosed as atypical lymphoid proliferation, and 4 of them initially incorrectly diagnosed as negative or progressive transformation of germinal centers (PTGCs). The flow cytometry studies showed similar expression patterns of CD57, CD4, and CD8 in T cells and very similar high percentages of CD57+ T cells and CD4+CD8+ T cells between initial biopsies and subsequent biopsies in these patients. Negative flow cytometry findings were seen in two specimens pathologically confirmed as negative for NLPHL in two patients after treatment. Their initial diagnostic specimens showed positive flow cytometry findings, different from that seen in the subsequent specimens posttreatment.

Conclusion
Flow cytometry appears to be a useful adjunct in detecting early or relapsed NLPHL, especially in atypical lesions. The presence of positive flow cytometry features is very sensitive in detecting recurrent or persistent NLPHL, while absence of positive flow cytometry features helps rule out NLPHL.
EBV-Positive Primary Large B-cell Lymphoma: Highlighting the Role of XPO1 in the Diagnosis of Mediastinal Lymphomas
Authors: Maracaja Danielle Lameirinhas Vieira , Puthenpura Vidya , Pels Salley , O’Malley Dennis , Sklar Jeffrey , Finberg Karin , Xu Mina 
Published: September 2019

Abstract

Background
Primary mediastinal (thymic) large B-cell lymphoma (PMBL) is described to be almost always negative for EBV in the current WHO. In the context of a mediastinal lymphoma, the distinction between PMBL, classic Hodgkin lymphoma (CHL), diffuse large B-cell lymphoma, and mediastinal gray-zone lymphoma can be very difficult; hence, EBV positivity often aids in pointing away from a diagnosis of PMBL. However, since EBV positivity can occur in rare PMBLs, it should not be the deciding factor in the diagnosis; assistance from molecular studies is emerging in these difficult cases.

Case Presentation
We present a 19-year-old male patient with a 2-week history of cough, vocal changes, and occasional dysphagia who was found upon imaging to have a 6-cm mediastinal mass. The biopsy of this mass was morphologically consistent with PMBL but the tumor was EBV positive by in situ hybridization.

Methods
We performed next-generation sequencing using Oncomine Comprehensive Assay v3 (ThermoFisher Scientific) on formalin-fixed, paraffin-embedded tumor tissue with a buccal swab sample for germline control. Variant calling, filtering, and annotation were performed by the Yale Tumor Profiling Laboratory.

Results
We found somatic mutations in XPO1, SMARCB1, and MYC. Along with classic immunophenotype of PMBL including positivity for MAL, OCT2, BOB1, BCL6, CD79a, MUM1, CD20, and subset weak CD30, the diagnosis was confirmed to be PMBL.

Conclusion
This is the first EBV-positive PMBL in which molecular profiling was performed. XPO1, specifically the mutation hotspot (E571K), found in our case is involved in PMBL and CHL. This was clinically helpful in confirming the histopathologic diagnosis and also opening up a targeted therapeutic option. Selective inhibitors of nuclear export (SINEs) that block the binding of XPO1 to its cargo are in clinical development as antineoplastic agents and have shown promising activity against some hematologic malignancies.
Three Cases of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Involving Cerebrospinal Fluid (CSF)
Authors: Shestakova Anna , Healey Jayne , Zhao Sheila (Xiaohui) , Rezk Sherif , Nakagiri Jamie 
Published: September 2019

Abstract

Background
Chronic lymphocytic leukemia (CLL) is a clonal disorder of B lymphocytes, characterized by proliferation of small mature lymphocytes involving the blood, bone marrow, and lymphoid tissues. CLL can rarely involve the central nervous system (CNS), either by involving brain parenchyma or cerebrospinal fluid (CSF). We present a series of three cases with clinically significant involvement of the CNS with CLL.

Results
During the past 2 years, our medical center managed three patients with CLL who presented with symptomatic CNS involvement, as determined by flow cytometry. The immunophenotypic profile was that of a typical CLL with light chain restricted small B cells positive for CD20 (dim) and coexpressing CD5 and CD23. In addition, two patients had brain involvement by SLL that was confirmed by brain biopsy. Notably, the brain lesions had a mildly elevated Ki-67 proliferative index (10%-30%). Bone marrow was involved in two patients, showing nodular, interstitial, and diffuse patterns. Bone marrow involvement ranged from 60% to 80% and showed very low Ki-67 proliferative index. None of the patients had features suggestive of a CLL transformation. FISH was performed on either bone marrow or CSF and demonstrated that patient 1 had Del11q(ATM) and Dell13q, patient 2 had trisomy 12, and patient 3 had del17(TP53) and IGH rearrangement. All of the patients showed persistent CSF involvement, ranging from 4 to 12 weeks, requiring aggressive treatment with intrathecal chemotherapy. At the end of treatment, all of the patients were clear of CNS involvement as judged by flow cytometry of CSF.

Conclusion
We report three patients who had persistent involvement of CSF. Only one patient had del17(TP53), a cytogenetic feature that is associated with high-risk CLL. It would be interesting to study clonal evolution of CLL to understand the mechanisms that underlie involvement of the CNS.
Effect of Temperature Fluctuation and Transport Time on Complete Blood Count Parameters
Authors: Kaur Amandeep , Lee Hong-Kee , Del Giudice Denisse , Singh Irene , Eldibany Mohamed 
Published: September 2019

Abstract

Introduction
Reliable specimen collection and transport are fundamental to obtain high-quality test results in the hematology laboratory. Recognizing the effect of fluctuations in transport and storage conditions, time, and temperatures on the integrity of specimens and quality of results may help define the optimal transport and storage parameters. We designed an IRB-approved quality improvement study to investigate the effects of temperature fluctuation and duration of storage on blood parameters.

Methods
Ten volunteers donated blood for the study. All samples were deidentified and volunteers were blinded to the results without any review of their charts. Eight EDTA vials were collected from each volunteer and were immediately stored in heating blocks/refrigerators/freezers at selected temperatures including 0°C, 2 to 8°C, 25°C, 30°C, 35°C, 40°C, 45°C and at room temperature (21°C). Blood parameters were then measured using sysmex XN series at 0, 8, 12, 24, and 48 hours and values were analyzed.

Results
We observed that total white cell count, Hb, MCH, and platelets were stable for 12 hours at 2 to 35°C. RBCs and MPV were stable for 12 hours at 2 to 30°C, whereas blood parameters including Hct, RDW, MCV, and MCHC were stable up until 12 hours at room temperature but not at higher temperatures. All parameters were stable at 2 to 8°C even up to 48 hours.

Conclusion
It is preferable to perform CBC on blood specimens as soon as they are received. However, our data suggest that most of the blood parameters are stable for at least 12 hours at room temperature. The integrity of specimens and consequently the quality of the results deteriorate above 35°C and when stored longer than 24 hours; 2 to 8°C is the optimal temperature range for specimen transport, especially if delays in analysis are anticipated.
Malodorous Skin Lesions in a Diabetic Patient: Infectious Versus Neoplastic
Authors: Elbaz Younes Ismail , Rewerska Julia , Alagiozian-Angelova Victoria 
Published: September 2019

Abstract
Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma is a rare entity accounting for <1% of all cutaneous T-cell lymphomas. Almost all patients present with generalized skin lesions. This type of lymphoma has an extremely aggressive course with a median survival of 12 months. It tends to spread to other visceral sites, but lymph nodes are usually spared. We describe a case of a 59-year-old male with multiple necrotic malodours ulcers for several months. The first lesion was on his left thigh, followed by another lesion on his right chest and right eyelid. Medical history revealed newly diagnosed diabetes mellitus. The patient received antibiotics, presumptively for infectious etiology of the skin lesion, with no improvement. The right thigh lesion was excised and histomorphologic examination revealed a deep dermal proliferation of large-sized pleomorphic cells with marked pagetoid epidermotropism and skin ulceration. The adnexal skin structures were invaded by the lesion. The lesional cells were immunoreactive for CD3, CD7, CD8, and granzyme B; they were negative for CD4, CD5, CD56, and CD30. The immunophenotype confirms the entity that we have at hand in addition to the similar clinical picture that the patient presented with. This disease usually shows clonal TR gene rearrangements; nonetheless, no specific mutational aberration has been described. Our patient received chemotherapy; however, new lesions continued to erupt and he opted to proceed with palliative care. Clinical information is needed to give this diagnosis as it may look identical to a variant of lymphomatoid papulosis (type D), CD8-positive cutaneous T-cell lymphoma. We present this case due to the importance of clinical pathologic coloration to prevent misdiagnosis with mimickers as the ones pointed out earlier, and it is a provisional rare entity in the 2018 WHO classification of Tumors of Haematopoietic and Lymphoid Tissues.
Familial Platelet Disorder/Predisposition to Acute Myeloid Leukemia With Germline RUNX1 Mutation Masquerading as Idiopathic Thrombocytopenic Purpura: Case Study
Authors: Reddy Kalpana 
Published: September 2019

Abstract
A 25-year-old female underwent emergent laparoscopic salpingectomy when she presented with an ectopic pregnancy (G1P0). A bone marrow biopsy performed for moderate persistent thrombocytopenia (60-105 K/μL) showed normocellularity, maturing trilineage hematopoiesis, and mildly increased morphologically normal megakaryocytes reported as consistent with idiopathic thrombocytopenic purpura (ITP). However, on further inquiry, the patient stated that her sister, father, paternal aunt, and paternal grandfather have/had low platelets. Her father had been diagnosed with myelodysplasia (MDS). Her paternal grandmother had died of acute myeloid leukemia (AML). Thus, although her marrow morphology revealed no evidence of overt dysplasia and despite her normal karyotypic study, a sample was sent for RUNX1 sequence analysis. A splice site mutation (c.967 + 2_967 + 5delTAAG) in RUNX1 was detected and initially interpreted as a somatic mutation. However, given the strong family history of thrombocytopenia and MDS/AML, a sample from her father was also sent for RUNX1 sequence analysis, and the identical intronic sequence variant in the RUNX1 gene was detected in him. This confirmed the RUNX1 mutation to be germline. In the context of autosomal dominant thrombocytopenia in the patient’s family, the finding of this variant in the affected patient and her similarly affected father was consistent with a pathogenic role. Since this patient was of reproductive age actively trying to have children, these molecular genetic findings had important implications. She elected to undergo in vitro fertilization in order to choose embryos without the RUNX1 mutation for implantation. Considering that her father and paternal grandmother developed MDS/AML, and because familial platelet disorder with predisposition to AML appears to show “anticipation,” she would require close future monitoring for blastic transformation. This case illustrates the significance of careful history taking and high suspicion index that can lead to simplified targeted cost-effective molecular testing resulting in the correct diagnosis without necessarily employing large gene panels.
Hemoglobin Phenotypes in Nigeria: Data From a National Reference Laboratory
Authors: Adewoyin Ademola , Busari Olusogo , Aworanti Oladapo 
Published: September 2019

Abstract
On a global scale, 5% to 7% of the population carries an abnormal hemoglobin. With a sickle hemoglobin (HbS) carrier prevalence of 25% to 40%, Nigeria bears the greatest burden of sickle cell disorder worldwide. Until recent times, detection of other clinically significant hemoglobin variants associated with HbS has been unavailable, resulting in missed/wrong diagnosis, weak national data, and suboptimal control of hemoglobin disorders. This study aimed to review hemoglobin assays over a 2-year period at a national reference laboratory in Nigeria, in order to describe the prevalent hemoglobin phenotypes for health planning. The study was a retrospective, laboratory data-based survey. Sociodemographics and hemoglobin assay results of 6,851 specimens between January 2016 and December 2017 were analyzed. Study protocol was approved by the Institutional Review Board. Participants aged less than 1 year and who had recent transfusions and a history of hydroxyurea therapy were excluded. At the hemoglobin laboratory, specimens were analyzed using cation exchange high-performance liquid chromatography (CE-HPLC) (Bio Rad D10, California). When indicated, further analysis of suspected abnormal hemoglobins was confirmed using a second method, capillary electrophoresis (SEBIA Capiflex II, France). The distribution of the identified hemoglobin phenotypes was determined as a proportion of the total number of participants. The mean (SD) age of the participants was 31.8 (14.9) years. The most frequent hemoglobin phenotypes were AA (59.4%), AS (23.3%), and SS (13.3%). Hemoglobin phenotypes AC (2.1%), SC (0.9%), AGPhiladelphia (0.2%), and CC (0.2%) were less frequent. Least occurring phenotypes were ADIbadan, AE, AGPhiladelphia, AOArab, DD, and hereditary persistence of fetal hemoglobin (HPFH). In the Nigerian context, accurate diagnosis of hemoglobin variants using quantitative, high-resolution hemoglobin assays, compared to zone (cellulose acetate) electrophoresis at alkaline pH will provide data for health planning, better access to genetic counseling, informed reproductive health choices, and secondary prevention of hemoglobinopathies.
Determining if Residual Eosin From Dehydration and Clearing Solutions Has an Effect on Immunohistochemistry
Authors: Gardner Christine 
Published: September 2019

Abstract

Objectives
Immunohistochemistry is a diagnostic stain that gives more specificity in testing for a disease and/or condition of patient tissue. Moore Regional Hospital is on the cusp of the LEAN Principle and currently in the early stages. The histology laboratory encountered a “waiting waste” problem due to two areas of histology sharing a common instrument. It is proposed to create a protocol on the Tissue-Tek Prisma stainer specifically for running down immunohistochemistry slides using the same alcohols and xylenes within the current H&E staining protocol. Research is scarce on whether residual eosin, from the dehydrating and coverslip phase, has an effect on immunohistochemistry morphology.

Materials
Three trial runs were conducted using a cytokeratin immunohistochemistry control. Each trial had dependent variables of staining times, staining parameters, and the changes of alcohol and xylenes. Cytokeratin is a feasible slide to use considering time stipulations and due to its prominent positivity. The instruments used in this validation were the BenchMark Ultra and the Tissue-Tek automatic stainer. The reagents used in this validation were the DAB chromagen, Hematoxylin (Ventana), Bluing (Ventana), Xylene (Cardinal), and Alcohol (Cardinal).

Results
Interpretations concluded that residual eosin does not have any direct artifact or undesirable outcomes. However, minor findings were noted on how the depar solutions did affect the visual quality of the cytokeratin.

Conclusions
Pros and cons were discussed in terms of moving forward with this process and improving the overall quality of the histology laboratory. It was decided that the lab move forward with the process or automatically running immunoslides down in automatic stainer. The overall quality of the slides improved due to the decrease in human variability and there is time added for the IHC tech to complete other tasks.
Epidermoid Cyst in the Intrapancreatic Accessory Spleen: A Case Report and Review of the Literature
Authors: Nakanishi Yukihiro , Behl Preeti , Kadi Abida , Crawford Byron 
Published: September 2019

Abstract
Epidermoid cyst in the intrapancreatic accessory spleen (ECIAS) is an exceedingly rare nonneoplastic entity. It generally does not require therapeutic intervention, but it is often misdiagnosed preoperatively as a cystic tumor, such as a mucinous cystic neoplasm or a cystic degeneration in a solid pancreatic neuroendocrine tumor or solid pseudopapillary neoplasm. We herein report a rare case of ECIAS in a 33-year-old African American man with a history of end-stage renal disease secondary to IgA nephropathy, congestive heart failure, and sickle cell trait who was referred to our facility for a renal transplant workup. A contrast-enhanced abdominal computed tomography during the workup revealed a bilobed low attenuating mass (3.4 × 3.4 × 2.5 cm) in the tail of the pancreas. Because malignancy could not be excluded, the patient underwent a distal pancreatectomy and splenectomy. Gross examination of the surgical specimen revealed a smooth-walled, multiloculated cyst (3.7 × 2.7 × 2.0 cm), containing serous fluid within the pancreatic parenchyma. Microscopically, the cyst was lined by nonkeratinizing stratified squamous epithelium without skin appendages, surrounded by benign splenic tissue in the pancreatic parenchyma. No dysplasia or malignancy was seen. Immunohistochemically, the lining epithelium was positive for p63, CK5/6, and CEA and negative for CA19-9, which supports the above diagnosis. The postoperative course was uneventful. In conclusion, ECIAS is a rare benign entity that can mimic malignant conditions and should be considered in the differential diagnosis of cystic lesions in the tail of pancreas.
Frozen Sections of Sentinel Lymph Nodes From Breast Cancer Patients Who Undergo Neoadjuvant Therapy Are Accurately Diagnosed Using Telepathology
Authors: McMurtry Valarie , Factor Rachel 
Published: September 2019

Abstract

Objectives
Telepathology enables histologic diagnosis to be made from a scanned slide visualized on a computer. Frozen sections (FSs) can be performed at remote locations and read by a pathologist at a central site. At our institution, qualifying breast cancer patients are enrolled in clinical trials that require FS on sentinel lymph nodes (SLNs) after neoadjuvant therapy (NAT), including chemotherapy or endocrine therapy. In this setting, histology is complicated by treatment effect and biopsy site changes. Others have reported good accuracy of FSs on SLNs after NAT. We investigated whether pathologists are accurate in diagnosing SLN FSs for such cases while using telepathology. To our knowledge, this has not been reported previously.

Methods
SLNs were entirely submitted and serially sectioned (2-mm thickness). At least two levels were cut. All FSs were submitted for formalin-fixed, paraffin-embedded permanent sections. A pathology assistant at the remote location prepared the FSs and scanned slides using the VisionTek M6 digital microscope ecosystem (East Dundee, IL). Cases were interpreted by board-certified pathologists who completed training on the VisionTek system. For this study, diagnoses from FSs and permanents were compared.

Results
Forty-five SLNs from 19 breast neoadjuvant cases were read by VisionTek from March 2017 to January 2019. Forty-three cases (96%) called negative by FSs were confirmed negative (on permanents). One hundred percent called positive by FSs were positive. Four SLN called atypical on FSs were positive. Three of these were neoadjuvant endocrine cases for invasive lobular carcinoma. Two cases called atypical were negative. One of these, called atypical/suspicious, resulted in axillary dissection. This case was reviewed by three pathologists at the time of surgery. It had abundant treatment effect, mimicking carcinoma.

Conclusion
While pitfalls exist, overall, the diagnostic accuracy of frozen section analysis by telepathology of SLNs from breast cases after neoadjuvant therapy is high.
Quality Management: Institution of Incident Reporting in the Clinical Laboratory
Authors: Reeves Melissa , Ullah Ehsan , Hufnagel Robert , Tumminia Santa 
Published: September 2019

Abstract

Introduction
Risk assessment is a critical part of quality management for a clinical laboratory. As a part of risk management, it is important to track any deviances from standard operating procedures (SOPs) and document equipment or assay failures consistently.

Methods
Our laboratory instituted an incident reporting system for reporting any deviances from protocol or equipment failures to track recurrent issues and determine if changes to protocols were necessitated. A guidance for completing the form was used so that the forms were completed in a standardized manner. Each incident is given a unique ID for tracking and identifies who discovered the incident and a secondary person that the incident was reported to at the time of occurrence. The incident is classified as Process, Instrument, Personnel, or Other and could be grouped into more than one category. The Other category includes incidents such as those involving reagent or equipment malfunctions. Incident reports are reviewed and discussed during the weekly lab meeting to determine the most appropriate category(s) for classification. Further, a fixed decision-making algorithm was applied to intervene specifically if the incident (a) was recurring, (b) required an SOP investigation or additional personnel training, and (c) needed to be reported to the institutional review board (IRB). Incidents are tracked until corrective action has been completed and reviewed periodically by the laboratory director. We reviewed the data after our first year of incident reporting to evaluate trends in incident categories.

Results and Conclusion
Forty-nine incidents were reported December 2017-2018. The highest classification categories included Other and a dual category, Process and Personnel, with 10 reports in each (40.8% overall). Twelve incidents were considered Recurring, 16 prompted SOP updates, and 1 was reported to the IRB. Through incident reporting, we were able to identify and resolve key risk areas in our procedures, which improved our operations and overall quality.