bluuebunny/crossref_metadata_2025 huggingface dataset:
Osseous Metaplasia: An Unusual and Poorly Understood Finding in Gastric Polyps
Authors: Zayko Maria , Wheeler Yurong
Published: September 2019

Osseous metaplasia (OM) is an uncommon finding in gastrointestinal tract biopsies. Metaplastic bone formation has been predominantly reported in the lower GI tract in a background of benign and malignant neoplasms, as well as nonneoplastic inflammatory conditions. OM in the stomach is extremely rare, with less than 10 cases reported in the English literature to date. We present two cases of gastric OM encountered at one institution among more than 10,000 stomach polyps examined since 1994. The first is a 46-year-old female with spastic quadriplegia, peptic ulcer disease, and a jejunal feeding tube who had multiple gastric hyperplastic polyps removed over a 13-year period. The most recent polypectomy revealed a 3-cm gastric adenoma with benign bone formation in the stroma. The second case is of a 67-year-old asymptomatic male with a remote history of intestinal metaplasia and atrophy of the stomach who underwent upper endoscopy and removal of a 1-cm polyp. Sections consisted of hyperplastic foveolar epithelium with focal ossification. Both polyps showed acute and chronic inflammation and stromal fibrosis, and they lacked Helicobacter infection. Mechanisms driving gastrointestinal OM have been proposed since the first reported cases in the early 1900s. The most widely accepted theory is that osteogenic factors released by the neoplastic or inflammatory tissue induce undifferentiated stromal mesenchymal cells or fibroblasts to undergo transformation to osteoblasts. However, with gastrointestinal biopsies being one of the most common specimens, the picture remains incomplete as only very rare cases show bone formation, warranting further research. Although gastrointestinal OM appears to be clinically insignificant, long-term studies have yet to be performed. Nevertheless, it is crucial for pathologists to be aware of this phenomenon in order to avoid misdiagnosing OM as a primary mesenchymal neoplasm or bone invasion in cases of OM arising in the background of malignancy.
Histopathological Pattern of Prostate Cancer in a Tertiary Hospital in Ghana
Authors: Aboagye Evans , Asante Emmanuel , Owusu-Afriyie Felicia , Titiloye Nicholas , Duduyemi Babatunde
Published: September 2019

Objectives

Prostate adenocarcinoma (PCa) accounts for considerable morbidity in aging men in Africa. With fewer studies reporting on PCa within the subregion, this study was set out to analyze various clinicopathological patterns in PCa lesions, providing additional data for comparison with reported PCa cases in other parts of the globe.

Methods

The study included prostatic adenocarcinoma tissues received in the Department of Pathology, Komfo Anokye Teaching Hospital, over a period of 6 years (from 2008 to 2013). Relevant clinical data including age, histopathological diagnosis, and Gleason’s microscopic grading were extracted from the surgical day book of the department. In a consecutive order, archived tissue blocks and slides of the selected cases were also retrieved for review and confirmation of diagnosis.

Results

Mean age at presentation was 71.7 ± 8.72 years (age ranged from 53 to 96 years) with a peak in the seventh decade of life (n = 41, 52.6%). Majority of the cases were poorly differentiated (n = 43, 55.1%), followed by moderately differentiated (n = 20, 25.6%) and well-differentiated samples (n = 15, 19.2%). Highest occurrence of prostate adenocarcinoma was recorded in the year 2009 (n = 46), followed by 2008 and 2009 (n = 16 and 13, respectively), together accounting for 96.2% of the cases reported.

Conclusion

Histopathological evaluation of prostatic biopsies remains the mainstay of diagnosing prostate adenocarcinoma in Ghana. The pattern of incidence in the population is in line with several reported studies, with majority of the cases diagnosed at the late stage of the disease and thus portending worse prognosis.
Histiocytic Sarcoma in the Kidney: A Rare Presentation
Authors: Johal Priya
Published: September 2019

Background

Histiocytic sarcoma is a rare neoplasm of mature histiocytes with a wide range of clinical presentations and manifestations. The heterogeneity of this neoplasm can cause difficulty in both diagnosis and treatment. It is a diagnosis of exclusion, requiring verification of the histiocytic lineage and the exclusion of other B-cell related malignancies. Although cases of postrenal transplant histiocytic sarcoma have been reported, incidences in a native kidney are rare.

Case Report

We present the case of a 70-year-old male with a history of colorectal adenocarcinoma, status post chemotherapy, with an incidental exophytic renal mass found on imaging, which was determined to be a sarcomatoid renal cell cancer on biopsy. Radical nephrectomy was performed, revealing a 4.5 × 3.5 × 3.2-cm mass invading the renal pelvis and fat. Microscopic examination of the tumor showed large, poorly cohesive neoplastic cells with abundant pale, eosinophilic cytoplasm that stained positive for vimentin, CD4, CD163, and CD68 and weakly/focally positive for lysozyme. Negative immunostains included PAX-8, pan-CK, AE1/AE3, HMB45, S100, CD34, CD30, ALK1, CD1a, myeloperoxidase, CD138, myo-D1, SMA, and CD21. A diagnosis of histiocytic sarcoma, grade 4 was made based on these findings.

Discussion

Histiocytic sarcoma is a disease of unknown etiology accounting for less than 1% of all hematolymphoid neoplasms. Our literature review revealed no other cases arising de novo in the kidney, but several cases were reported in postrenal transplant patients.

Diagnosis of histiocytic sarcoma is difficult as it is a diagnosis of exclusion. The immunohistochemical profile most often expresses lysosome-related markers, such as CD68, CD163, or lysozyme. Additionally, negative staining is expected for markers related to B cells, T cells, and melanocytes. The cells are often large with eosinophilic cytoplasm, well-defined borders, and vesicular chromatin. Although there are numerous differentials, distinct morphologic and immunohistochemical features allow for accurate diagnosis.
Validation of a Thiocyanate Method on the Shimadzu UV-1800 Spectrophotometer
Authors: Zot Patricija , Gin Gregory , Bachmann Lorin
Published: September 2019

Objectives

Sodium nitroprusside is used in treatment of hypertensive emergency. In the body, nitroprusside is metabolized to cyanide and cyanide to thiocyanate. Thiocyanate concentration is used to monitor nitroprusside therapy and to evaluate possible exposure to cyanide. A method validation study was performed to assess analytical performance of a new spectrophotometry-based laboratory-developed test for serum thiocyanate.

Methods

Serum proteins were precipitated using trichloroacetic acid and ferric nitrate. The resulting red-colored solution was measured spectrophotometrically at 450 nm using the Shimadzu UV-1800 spectrophotometer (Shimadzu Scientific Instruments, Columbia, MD). Method precision, linearity, method comparison, and effect of interferences were evaluated according to Clinical Laboratory and Standards Institute guidelines. The Microsoft Excel Analyze-It application was used for statistical analysis.

Results

Between-run coefficients of variation (CVs) for quality control materials at thiocyanate concentrations of 5 mg/L, 20 mg/L, and 50 mg/L were 9.64%, 6.26%, and 4.25%, respectively. The assay was linear over the analytical measuring range of 5 mg/L to 200 mg/L, with an r2 value of 0.9982. The Deming regression equation for the UV-1601 (comparator) and UV-1800 (new) method was: UV-1800 = 0.998 (95% CI, 0.9762-1.001) UV-1601 + 0.79 (95% CI, –0.1379 to 1.733), and the standard error of the regression was 1.8 mg/L. Interference of <7% was observed in the presence of hemolysis, icterus, and lipemia.

Conclusion

The analytical performance of the new Shimadzu UV-1800 spectrophotometer method is adequate for measurement of serum thiocyanate in patients on nitroprusside therapy or with cyanide poisoning.
A Report of Submucosal Intravascular Paraganglioma of the Gallbladder and Review of the Literature
Authors: Bennett Brian , Webb David
Published: September 2019

Objectives

The purpose of this case study and review of the literature is to allow pathologists to recall an appropriate differential diagnosis for submucosal epithelial tumors of the gallbladder. It is also important to note the immunohistochemical evaluation of a paraganglioma.

Methods

Intraoperative findings were multiple adhesions of the omentum to the gallbladder itself, with a mildly dilated cystic duct measuring 6 to 7 mm externally. The intraoperative cholangiogram was normal with no evidence of retained stones. The gallbladder was 9.5 cm and essentially unremarkable with no stones upon gross examination. Palpation revealed a 5 × 4 × 4-mm gray-tan cystic duct lymph node that was microscopically unremarkable. Microscopically, there was a 2.7-mm submucosal intravascular epithelioid tumor. Cytologically, the cellular infiltrate was cohesive, filled, and expanded a single submucosal vessel. A broad panel of immunohistochemical stains was performed, with the results listed below.

Results

Carbonic anhydrase IX: Negative; Monoclonal CEA: Negative; CK7: Negative; CK 20: Negative; Gata-3: Positive; Mart-1: Negative; OCT3/4: Strong diffuse positive; P 63: Negative; Pancytokeratin: Negative; PAX-8: Negative; S-100: Negative; WT1: Negative; PLAP: Negative; Hep par 1: Negative; AFP: Negative; CD117: Negative; CD 30: Negative; CDX2: Negative; Glypican 3: Negative; SALL4: Negative; Inhibin: Negative ERG: Negative; CD34: Negative; CD56: Strong diffuse positive; Synaptophysin: Strong diffuse positive; Chromogranin: Strong diffuse positive.

Conclusion

Expert opinion was requested to confirm the presumed diagnosis on this case. The consulting pathologist was in agreement that this was best classified as an intravascular paraganglioma. The patient was seen in follow-up and a CT of the chest, abdomen, and pelvis was ordered. Interestingly, a 1.9-cm enhancing upper pole right renal mass was identified. The patient was sent to urologic surgical consultation in which they believed this tumor to represent a stage 1a primary renal cell carcinoma and subsequently sent for radiofrequency ablation.
Androgen Receptor Overexpression in Patients With Prostate Cancer in Kampala, Uganda
Authors: Yahaya James , Ajok Florence , Odida Michael , Wabinga Henry
Published: September 2019

Objectives

This study was aimed at determining the status of androgen receptor overexpression in patients with PCa and also correlating overexpression with Gleason score, patient age, and prostate-specific antigen (PSA).

Methods

This was a cross-sectional analytical laboratory-based study using retrospectively retrieved formalin-fixed, paraffin-embedded (FFPE) tissue blocks of 93 PCa patients who were diagnosed histologically between January and December 2018. Immunostaining was done using AR antibody. Cases with ≥10% positive cells having staining intensity of +1 and above were considered positive. Confirmation of the histological diagnosis and interpretation of the IHC-stained slides were done by two independent expert pathologists in a blinded manner. The association between AR overexpression and categorical variables was tested using the chi-square test, while continuous variables were tested using the t test with a 95% confidence interval (CI). A P < 0.05 was taken as statistically significant.

Results

AR overexpression was found in 54.8% (51/93) of the cases in this study. Majority of patients, 73.1% (68/93), had a Gleason score of 8 to 10, whereas a Gleason score of 6 to 7 was found in 26.9% (25/93). The mean Gleason score for the cases was 8.47 ± 1.52. Patients with a low Gleason score (≤7) had a higher proportion of AR overexpression than those with a high Gleason score (>8) and the difference was statistically significant (P = .013).

Conclusion

The clinical relevance of this study was that AR overexpression is associated with a Gleason score but not with age and prostate-specific antigen (PSA). AR overexpression was an independent predictor of PCa prognosis.
Application of the CLSI EP15-A3 Guideline as an Alternative Troubleshooting Tool for Verification of Assay Precision
Authors: Aguirre Jose Jara , Ness Karl , Algeciras-Schimnich Alicia
Published: September 2019

Introduction

The CLSI EP15-A3 guideline “User Verification of Precision and Estimation of Bias” provides a simple experimental approach to estimate a method’s imprecision and bias. The objective is to determine if the laboratory precision performance of repeatability (SR) and within-laboratory imprecision (SWL) are in accordance to the manufacturer specification claims (MSCs).

Objectives

Evaluate the utility of the EP15-A3 protocol to verify method precision during a troubleshooting investigation and after major instrument maintenance, using a carcinoembryonic antigen (CEA) immunoassay as an example.

Methods

CEA was performed on the Beckman Coulter DxI (Beckman Coulter, Brea, CA). Quality control (QC) levels (L1: 2.89; L2: 21.10; L3: 39.10 ng/mL) (Bio-Rad Laboratories, Irvine, CA) were used. Each QC level was measured before and after instrument maintenance as follows: five replicates per run, one run per day, and during 5 days. Imprecision estimates (IEs) for SR (%CVR) and SWL (%CVWL) were calculated by one-way analysis of variance using Microsoft Excel Analyse-it software. Estimated imprecision was compared to MSC and desirable imprecision specifications based on biological variation (BV).

Results

A change in the analytical performance of CEA was detected by a decreased sigma-metric indicator. After a bias problem was ruled out, the observed %CVR for L1, L2, and L3 were 7.2%, 3.7%, and 4.8%, respectively. The %CVWL were 8.3%, 5.0%, and 5.5%, which exceeded the MSC of %CVWL~4.0% to 4.5%. After a laboratory investigation, major instrument maintenance was performed by the manufacturer. The %CVR and %CVWL estimates for L1, L2, and L3 after maintenance were 3.2%, 3.8%, 3.5% and 3.9%, 4.2%, 4.0%, respectively. After maintenance, the CEA performance was consistent with the MSC for each of the levels analyzed and within the BV impression goal of %CV ≤6.4.

Conclusion

CLSI EP15-A3 guideline is an alternative troubleshooting tool that can be used to investigate and verify method precision performance before and after significant instrument maintenance.
Advantages of the Use of Alcor iSED Automated Sed Rate Analyzer vs Manual Sed Rate in Evaluation and/or Monitoring the Treatment in Patients, CMCVAMC Experience
Authors: Patel Sahilkumar , Jhala Darshana
Published: September 2019

Objectives

The automated Alcor iSED automated instrument has a major impact on the proper management of the patients in a timely manner with use of a minimal amount of the blood (100 µL). The Alcor iSED analyzer has introduced a new technology that forgoes sample preparation by using a Load and Go technology. We were previously using the Westergren tube method, which required special preparation of the tube to load into a special provided sealed cup. The entire procedure was tedious and time-consuming. To overcome, we acquired and implemented the Alcor iSED analyzer for an efficient and prompt reporting of sedimentation rate.

Methods

A sample was aspirated and dispensed from a closed tube, then dispensed into a capillary, and quantitative capillary photometry (aggregation) was used to measure ESR faster than traditional methods by capturing the kinetics of red blood cell aggregation in a controlled testing environment during the most critical phase of sedimentation, commonly referred to as the lag or Rouleaux formation phase. As a part of quality assurance monitoring, retrospective split analysis was performed for 75 samples. Analysis was performed using a Passing-Bablok regression analysis with the MedCalc program.

Results

Our results demonstrated significant differences between the two methods for the TAT. The TAT was significantly decreased with Alcor iSED (3 minutes for the first specimen and then 15-20 seconds for each sequential specimen) as compared to the manual Westergren method (1 hour), which significantly improved the reporting of results to the providers to monitor the treatment.

Conclusion

The Alcor iSED analyzer has provided truly shortened TAT erythrocyte sedimentation rate, allowing for better patient care and treatment.
Impact of the Opioid/Fentanyl Epidemic on the Toxicology Laboratory’s Workload: The CMCVAMC Experience
Authors: Petersen Jeffrey , George Thomas , Jhala Darshana
Published: September 2019

Introduction

Opiates have long been used by both the population at large and the veteran population as a drug of abuse. However, recently, fentanyl—a synthetic opioid—has risen in prominence in this opioid drug abuse epidemic as a drug used by suppliers to “cut” heroin, to masquerade for another opiate, or for direct usage. As this is a recent phenomenon, the new increasing need to test for fentanyl for clinical reasons has a major impact on the toxicology laboratory’s workload.

Method

Quality assurance/improvement data were obtained to determine the number of fentanyl tests by gas chromatography/mass spectroscopy (GC/MS) performed by the toxicology laboratory since quarter 1 of 2011 (October-December 2010) to quarter 1 of 2018 (October-December 2017). The numbers of tests required for clinical care in each quarter were tabulated and compared in a graph. Quarters for each year begin and end in October.

Results

The total number of GC/MS tests for fentanyl needed for clinical care has been drastically increasing recently. From 2011 to 2015, the yearly number of tests clinically needed has ranged from 83 to 92. In 2016, the total number of clinically needed tests for fentanyl spiked to 167 and by fiscal year 2017 included 1,108 fentanyl GC/MS tests. The last examined quarter (quarter 1 of fiscal year 2018) included 527 tests, which is more than the highest number from 2017 (377 in quarter 4 of 2017).

Conclusion

The increasing use of fentanyl in the opioid epidemic appears to have played a role in significantly increasing the clinical need to test for fentanyl by GC/MS, increasing the volume by over 10 to 15 times. The role of fentanyl in the opioid epidemic remains a significant public health concern.
PD-L1 Immunohistochemistry on Cell Block Preparations From Different Fixatives: A Pilot Study
Authors: Costa Victoria , Kim David , Goyal Abha , He Bing , Liu Yifang , Rao Rema
Published: September 2019

Objectives

Immunohistochemistry especially for biomarkers such as PD-L1 in personalized medicine is increasingly being performed on cell blocks from cytopathology samples. We evaluated the effects of staining cell blocks (CBs) from different cytologic fixatives using four different commercially available PD-L1 antibody clones.

Methods

PD-L1 immunohistochemistry (IHC) using four different commercially available clones was performed on eight cell blocks processed from two different fixatives and also on eight formalin-fixed tissues. The clones used were 22C3 at 1:50 dilution and 1:100 dilution, SP263, SP142, and E1L3N. The cell block (CB) samples contained cells that strongly express PD-L1 and either fixed in CytoLyt (methanol-based fixative, n = 4) or CytoRich (ethanol-formalin-based fixative, n = 4). Formalin-fixed control tissues (tonsillar tissue, n = 4; stomach, n = 4) were also included.

Results

Expression for PD-L1 was noted on all the CytoRich fixed cell blocks (n = 4) for all four antibody clones, with the intensity and distribution of expression comparable to the formalin fixed tissues (n = 8). However, consistent absence of expression for PD-L1 was noted on all the CytoLyt fixed cell blocks (n = 4) for all four antibody clones.

Conclusion

The results of this pilot study demonstrate that PD-L1 IHC on cell blocks is feasible. However, there is a need to validate IHC protocols according to specific fixation methods.
IL-15 as an Immune Modulator in Schistosomiasis
Authors: Reust Mary
Published: September 2019

Introduction

Schistosomiasis affects approximately 200,000,000 people globally, with 93% of these cases in sub-Saharan Africa. Women who have been infected with Schistosoma haematobium have four times the risk of contracting HIV due to a change in their cervical mucosal immunity. The mechanism for this altered cervical mucosal immunity was not understood until a recent study published by Downs et al, which showed IL-15 levels were significantly lower in cervicovaginal lavage fluid samples of women with Schistosoma haematobium. Schistosoma mansoni, known to cause intestinal schistosomiasis, has also shown the potential to increase the risk of contracting HIV. The objective for this study is to see if IL-15 levels in peripheral blood are significantly different between patients positive for S mansoni and negative controls.

Methods

Enzyme-linked immunosorbent assays (BD Biosciences, San Jose, CA) for IL-15 were performed on plasma collected from 84 patients in villages in sub-Saharan Africa. These samples were collected at screening, 3-month follow-up, 6-month follow-up, and 9-month follow-up appointments.

Results

Of 249 plasma samples tested, 20 had detectable IL-15 levels ranging from 8.329 pg/mL to above the upper limit of detection of 500 pg/mL. While the patients that had detectable IL-15 in the peripheral blood were half S mansoni negative and half S mansoni positive, when an S mansoni–positive patient was positive for IL-15, it was across all timepoints.

Conclusion

The role of IL-15 as an immune modulator can explain the elevated levels in S mansoni–positive patients. All patients in the study were tested for significant comorbidities, with no correlation seen within the negative controls. Further testing is needed to investigate the role of IL-15 in the alteration of localized areas of infection with both Schistosoma mansoni and Schistosoma haematobium. More samples are currently being collected from the patient population in Tanzania, and future studies are planned.
Immunohistochemical Expression of BCL10 and Three Markers in Extranodal Marginal Zone Lymphoma and Other Small B-Cell Lymphomas
Authors: Zhang Xiaohong
Published: September 2019

Extranodal marginal zone lymphoma (EMZL) is a low-grade B-cell lymphoma representing about the third most common non-Hodgkin lymphoma in the Western world. EMZL shows heterogeneous morphological features and expresses no specific immunohistochemical markers except B-cell markers. BCL10 and MALT mutations causing NF-kB pathway activation play an important role in oncogenesis of EMZL. Aberrant nuclear expression of BCL10 is reported in some EMZLs. Nuclear expression of BCL10 has not been well compared between EMZL and other small B-cell lymphomas. The aim of this study is to evaluate the expression of BCL10 and three markers in different small B-cell lymphomas. Tissue microarray blocks and selected tissue blocks, formalin fixed and paraffin embedded, were selected for immunohistochemical (IHC) studies. More than 100 cases of different small B-cell lymphomas include EMZL, small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), and hairy cell leukemia (HCL) in the bone marrow biopsy. Commercially available antibodies from DAKO for BCL-10, IRTA-1, LEF-1, and SOX-11 were used according to the protocol. Immunoreactivity in greater than 20% of the tumor cells was considered positive. BCL-10 nuclear expression occurred mostly in EMZL but also in other small B-cell lymphomas except LPL and HCL. Cytoplasmic expression of IRTA-1 was detected in all cases of EMZL and also in SLL, MCL, and FL cases; it was negative in LPL and HCL. Nuclear expression of LEF-1 was detected mostly in SLL cases, a few cases of MZL, and none of the cases of MCL, FL, LPL, and HCL. Nuclear staining of SOX11 was found in most MCL cases; it was negative in all cases of SLL, EMZL, FL, LPL, and HCL. The IHC markers of BCL-10, IRTA-1, LEF-1, and SOX11 increase our ability to make accurate diagnosis of small B-cell lymphomas.
A Case of Langerhans Cell Histocytosis Masquerading as a Colon Polyp
Authors: Bishop Bradie , Lynch David , Brady Robert
Published: September 2019

Langerhans cell histocytosis, otherwise known as eosinophilic granuloma, is a rare neoplastic process composed of Langerhans cells and eosinophils. Most cases present during childhood, with the bones and skin being the most common organs involved. Other organs are occasionally involved, with some systemic cases involving the gastrointestinal tract. Presentations of Langerhans cell histocytosis range from single-organ involvement to systemic involvement. Fewer than five cases of isolated Langerhans cell histocytosis in the gastrointestinal system in adults have been reported.

We present a case of Langerhans cell histocytosis incidentally discovered during routine colonoscopy in a 67-year-old otherwise healthy woman. Initial colonoscopy performed 7 years prior demonstrated a sessile serrated adenoma, fragments of tubular adenomas, and hyperplastic polyps. Repeat colonoscopy 3 years later demonstrated a sessile serrated adenoma and hyperplastic polyp. Upon repeat colonoscopy 4 years later, the patient had nine subcentimeter polyps. One of the ascending colon polyp fragments demonstrated a well-circumscribed, submucosal nodule of granular pink histocytes with folded to clefted and reniform nuclei. Numerous eosinophils were present in the background. These findings were consistent with Langerhans cell histocytosis. The remaining polyps were a tubular adenoma and hyperplastic polyps. A CT chest/abdomen/pelvis did not demonstrate any evidence of systemic disease. One year postdiagnosis, the patient had not had recurrence of symptoms.

Unifocal Langerhans cell histocytosis rarely presents in the gastrointestinal tract of an adult and is believed to have a good prognosis with limited recurrence. The patient is being closely followed for development of systemic disease.
Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma Concomitant With Non-IgM Plasma Cell Neoplasm: Report of 5 Cases With Laboratory Evidence of Biclonal B-Cell Neoplasms in Single Individuals
Authors: McCracken Jenna , Neff Jadee , Zhao Yue , Wang Endi
Published: September 2019

Introduction

Plasma cell neoplasm (PCN) is rarely associated with Waldenstrom macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL), and its clonal relationship to WM/LPL is unclear.

Methods

We retrospectively analyzed five cases of PCN concomitant with WM/LPL for clinicopathologic features.

Results

Of five patients, three were female and two were male with a median age of 75 years at diagnosis of concurrent PCN-WM/LPL. Three cases presented with serum paraprotein of IgM type and had a diagnosis of WM/LPL before identifying concurrent PCN, with an interval of 1 to 10 years. In the remaining two cases, PCN and WM/LPL were concurrently diagnosed. All patients demonstrated biclonal M-spikes with distinct heavy chain isotypes but concordant light chain isotype (kappa or lambda) by immunofixation electrophoresis. In all four cases, two neoplastic populations were highlighted with immunohistochemistry, including expression of CD56/cyclin D1 (1), cyclin D1 (2), and IgA (1) in neoplastic plasma cells and negativity of CD56/cyclin D1 in LPL. Of three patients with clinical information available, two were treated with chemotherapy, and the other was treated with autologous stem cell transplant. At follow-up, one patient died of PCN progression at 24 months, one had recurrent WM/LPL at 144 months, and the other was alive with disease 5 months after the diagnosis of concurrent neoplasms.

Conclusion

Discordant heavy chain isotype restrictions between PCN and WM/LPL suggest biclonal B-cell neoplasms, which is supported by PCN’s phenotypic distinction, such as expression of cyclin D1 and/or CD56, from coexisting WM/LPL. However, our cases had WM/LPL either preceding or concurring with PCN, and all exhibited concordant light chain restrictions, raising a possibility that PCN may be evolved from WM/LPL with class switching. This issue of clonal relationship between the two B-cell neoplasm and underlying pathogenesis remains to be investigated with sequencing analysis on sorted PCN or WM/LPL and comparison of mutation profiles between them.
Evaluation of a 42-Gene Next-Generation Sequencing Panel for Detection of Acute Myeloid Leukemia Mutations for Clinical Use
Authors: Rosenthal Sun Hee , Gerasimova Anna , Ma Charles , Sugganth Daniel , Racke Frederick , Lacbawan Felicitas
Published: September 2019

Objectives

Identification of genetic alterations by molecular and cytogenetic testing has an important role in the classification, risk stratification, and management of acute myeloid leukemia (AML). We evaluated a next-generation sequencing (NGS) panel that assesses IDH2, FLT3, NPM1, and TP3 and 38 other genes associated with diagnostic, prognostic, and/or therapeutic utility in AML, with a turnaround time of 8 to 14 days, using a DNA input of 50 ng.

Methods

In total, 110 patients, 65 males and 45 females, at a median age of 58 years (range: 2-68 years) with clinical diagnosis of AML were included in this study. Targeted regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. Sequence reads were analyzed using a bioinformatics pipeline that was developed in house. Analytical sensitivity of the assay is ~5% mutated alleles with 100% specificity.

Results

A total of 296 pathogenic mutations in 38 genes were detected in 95 of 110 samples (86%). On average, three mutations (range 1-10) were detected per positive sample. Variant frequency ranged from 3.0% to 96.1%. Most frequently mutated genes were TET2 (18.2%), FLT3 (18.2%), TP53 (17.3%), RUNX1 (15.5%), NPM1 (14.5%), ASXL1 (12.7%), NRAS (11.8%), and CEBPA (10.9%). In total, 166 of 296 (56%) mutations from 13 genes had prognostic significance, 42 of 296 (14%) mutations from three genes (CEBPA, NPM1, RUNX1) had diagnostic significance, and 40 of 296 (14%) mutations from three genes (IDH1, IDH2, FLT3) had therapeutic significance.

Conclusion

This focused 42-gene targeted panel identifies mutations of clinical significance in over 85% of patients with a clinical diagnosis of AML.
Clear Cell Odontogenic Carcinoma of the Maxilla: A Case Report With Emphasis on Differential Diagnoses
Authors: Taherian Mehran , Alhazmi Yaser , Baqai Saad
Published: September 2019

Objectives

Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic epithelial neoplasm composed mainly of clear cells. It was first described in early 1980s with great uncertainty of its behavior. Nearly 100 well-characterized cases have been reported to date with mean age at presentation of 54 years and female-to-male ratio of 1.6:1. It shows greater predilection for mandible compared to maxilla. Herein, we present a case of CCOC arising in maxilla and discuss the clinicopathologic presentation with emphasis on the potential differential diagnoses of other head and neck clear cell tumors (HNCCTs).

Case Presentation

A 68-year-old male presented with facial swelling and hard palate bleeding. CT scan revealed large destructive mass at the floor of right maxillary antrum with involvement of hard palate. Biopsy showed invasive carcinoma with squamous differentiation and focal keratinization. No evidence of lymph node metastasis was noted radiographically. The patient subsequently underwent total maxillectomy with complete resection of the tumor.

Results

Histologic sections revealed tumor arranged in lobular islands showing biphasic morphology including peripheral palisaded hyperchromatic basaloid cells and central clear to faintly eosinophilic cells with well-demarcated cell membranes. The intervening stroma was fibrous and showed hyalinization. The diagnosis of CCOC was made on the basis of tumor morphology in conjunction with EWSR1 gene rearrangement, which was detected by fluorescence in situ hybridization (FISH).

Conclusion

CCOC, although rare, should be considered in the differential diagnosis of tumors with a clear cell component. It can mimic a variety of HNCCTs, particularly clear cell variant of squamous cell carcinoma, clear cell tumors from minor salivary glands, or metastases from other sites. These tumors can be locally aggressive with a relatively high recurrence rate. Pathologists should be cognizant of this entity with other HNCCTs and the use of proper ancillary testing to avoid potential pitfalls.
The Use of One Normal Hydrochloric Acid as a Background Cleaner for Periodic Acid–Schiff Staining Technique
Authors: Iyiola Sina , Adegoke Aremu , Adeleke Samuel
Published: September 2019

Objectives

Sulfurous rinsing was considered nonessential as contained in the published periodic acid–Schiff technique because it did not clear the background better than tap water washing. The objective of this work is to elucidate the use of 1N HCl as a better background cleaner in the periodic acid–Schiff staining technique.

Methods

This is an experimental research. Normal samples of antrium, kidney, spleen, muscle, liver, and appendix, as well as histopathologically diagnosed samples of glycogen storage disease of the liver, alpha-1-antitrypsin deficient liver, aspergillosis nasal cavity sample, and glomerulosclerosis samples were obtained from the pathological archive. These samples were stained with a newly purchased commercially prepared Schiff reagent and overstained commercially prepared Schiff’s solution causing nonspecific background staining and laboratory-prepared Schiff reagent. Oxidation was done with 1% periodic acid for 5 minutes, washed for 5 minutes with distilled water, and stained for 10 minutes in Schiff’s reagent, but 20-minute staining was observed for the overstained Schiff reagent, oxidized in running tap water for 15 minutes. It was then rinsed in 1N HCl for 20 seconds, washed in tap water for 2 minutes, and counterstained with hematoxylin for 2 minutes. The same procedure was done for another set of slides as standards without 1N HCl rinsing done. The slides were examined under the microscope and compared for specificity.

Results

Slides rinsed in 1N HCl showed a clear differentiation of strong, weak, and non-PAS-positive substances. The overall effect of these staining characteristics was more pronounced in the use of laboratory-prepared Schiff.

Conclusion

The use of 1N HCl as a differentiator made the PAS technique more specific in its staining characteristics, especially with the use of laboratory-prepared Schiff’s reagent, which is commonly used in developing countries owing to a high cost of commercially prepared Schiff’s solution.
Umbrella Cells Mimicking Focal High-Grade Urothelial Carcinoma in Low-Grade Papillary Urothelial Carcinoma
Authors: Hassan Muhammad Masood , Naab Tammey , Afsari Ali
Published: September 2019

Objectives

Low-grade papillary urothelial carcinoma (LGUC) has overall a preserved orderly appearance, minimal variability in architecture, and lack of significant cytologic atypia and mitotic activity without pleomorphism. A total of 53.8% of LGUC cases recur with 18.3% progression to high-grade UC. Even focal HGUC in LGUC can be a harbinger of progression. Accurate pathological interpretation is paramount in predicting recurrence and determining treatment.

Methods

A 63-year-old male with a past medical history of coronary artery disease, benign prostate hyperplasia, and obesity was referred to urology with a chief complaint of chronic hematuria. Cystoscopy with transurethral resection of bladder tumor was performed, which revealed mainly LGUC with focal high-grade-appearing UC.

Results

Histologic sections revealed papillary architecture with fused fronds, low-grade nuclear atypia, and scattered mitoses comprising 95% of the tissue submitted. No muscular wall invasion by carcinoma was seen. However, in one section, collections of large cells with well-defined cytoplasmic borders, multinucleation, and rare nuclear grooves were identified. The morphology raised the suspicion of a focal HGUC. Diffuse expression of CK20 and low Ki-67 proliferation index (1%) favored umbrella cells.

Conclusion

Our case reinforces the fact that sectioning can reveal foci, suspicious for HGUC, especially in urothelium. However, proper interpretation of morphology combined with the help of immunohistochemistry aids in accurate diagnosis, which is critical in determining proper clinical management of the patient.
HIT: Anti-Platelet Factor 4-Heparin (PF4-H) Assay Validation and Comparison Study
Authors: De Luna Mark
Published: September 2019

Objectives

The aims of the study were to perform an instrument validation of the HemosIL HIT-Ab (PF4-H) Assay and to compare the sensitivities and specificities of the three HIT tests (HemosIL HIT-Ab [PF4-H] Assay, PIFA Heparin/PF4 Assay, and Immucor PF4 ELISA) versus the gold standard Serotonin Release Assay performed in ARUP Laboratories and versus each other.

Methods

The HemosIL HIT-Ab (PF4-H) Assay was validated on the ACL TOP 750 using calibrators, controls, and samples from UF Pathology Laboratories and ARUP Laboratories that were previously tested for the HIT-Ab IgG via an ELISA method. EP Evaluator was used to calculate statistical data.

Results

A total of 116 samples were assayed using the HemosIL HIT-Ab (PF4-H) Assay and the PIFA Heparin/PF4 Rapid Assay. Overall, there were 125 positive tests and 255 negative tests for anti-PF4-H (ACL

TOP

39 positive, 77 negative;

PIFA

11 positive, 105 negative;

ELISA

60 positive, 56 negative). There were 15 positive and 17 negative for the SRA. The comparison between the ACL TOP and SRA had a sensitivity of 80.0% and specificity of 35.3%. ELISA vs SRA had a sensitivity of 100.0% but had a 0.0% specificity. The PIFA vs SRA correlation had a sensitivity of 0.0% and specificity of 88.2%. The ACL TOP versus UF Health’s current HIT ELISA method had a good comparison as well, with a sensitivity of 61.7% and a specificity of 96.4%.

Conclusion

The three HIT methods (ACL TOP, ELISA, and PIFA) compared to the SRA showed that the ACL TOP had a good positive agreement, but poor negative agreement; however, the ACL TOP had a very good negative agreement with the ELISA method. The PIFA cartridge test had an overall poor performance with no positive agreement with the SRA and poor sensitivity versus the ACL TOP and ELISA methods.
Improving Patient Value Through Cross-Country Collaboration
Authors: Yip Tameson , Ford Jennifer , Ramsower Colleen , Glinsmann-Gibson Betty , Robetorye Ryan , Rimsza Lisa
Published: September 2019

Introduction

Lymph2Cx lymphoma cell-of-origin assay (LM2CX) was developed by the Lymphoma/Leukemia Molecular Profiling Project (LLMPP) to better categorize diffuse large B-cell lymphoma (DLBCL). NanoString has licensed the assay and is currently pursuing FDA approval. In the meantime, the test is offered exclusively as a lab-developed test (LDT) by the Mayo Clinic Molecular Diagnostics–Arizona Lab (MDAZL) to Mayo Clinic Enterprise patients. In order to comply with these restrictions, the normal workflow for Mayo Clinic Rochester has been modified as cases are sent to Arizona. Rochester consultants order LM2CX using their local laboratory information system (LIS). Slides are prepared by Rochester histology and then shipped to Arizona, where they are entered into the Arizona LIS and processed. In July 2018, we discovered numerous cases that were ordered but not shipped. Because this step took place at the LIS transition between Arizona and Rochester, it was not detected immediately.

Methods

Allied Health Staff (AHS) colleagues in Rochester and Arizona had the unique opportunity to collaborate. After Arizona AHS identified the problem, they reached out to the Rochester pathology reporting specialists (PRSs) and began a joint improvement project. Together, we were able to measure the impact of the problem, with Arizona auditing digitally, while Rochester audited physical cases. We found 29% of the cases were handled improperly over a 6-month time period. In order to eliminate the gap, Rochester implemented several improvements, including training, tagging all LM2CX cases, and huddle discussions, while Arizona AHS monitored the process digitally.

Results

Since implementation of improvements, we have had zero defects. Modifications to AHS/consultant training in Rochester will ensure continued success.

Conclusions

This intervention illustrates the importance of strong collaborations in order to quickly respond to testing issues and provide the greatest value to patients.
Prevalence of Urinary Tract Infections (UTIs) Among Pregnant Women Attending Antenatal Clinic at Ile-Ife, Southwestern Nigeria
Authors: Onifade Jaiyeola , Oladipo Adegboyega
Published: September 2019

Objectives

This is a prospective study that reports the prevalence of urinary tract infections (UTIs) and the bacteriological causative agents among pregnant women attending antenatal clinics at a secondary care hospital in Ile-Ife, southwestern Nigeria. In total, 335 midstream clean-catch urine samples were collected from pregnant women between April and July 2017.

Methods

These were cultured for the presence of bacterial pathogens. All the isolates were subjected to antibiotic sensitivity testing on Mueller Hinton agar by a modified Kirby-Bauer disk diffusion technique using CLSI guidelines. Data were analyzed using SPSS for Windows version 16 and WHONET 5.

Results

A total of 190 showed significant bacterial growth while 145 showed no significant bacterial growth. Bacterial agents isolated included Klebsiella spp. showing the highest occurrence of 60 (31.5%), followed by Escherichia coli and Staphylococcus aureus with prevalences of 49 (25.7%) and 32 (16.8%), respectively. Other organisms implicated are Proteus mirabilis (20 [10.5%]), coagulase-negative staphylococci (24 [12.3%]), and Pseudomonas aeruginosa with the least prevalence (5 [2.6%]). They have a resistance to antibiotics such as amoxycillin (64%), gentamicin (52.6%), erythromycin (62.5%), ceftazidime (69%), cefotaxime (74%), and ceftriaxone (79.6%) but a high sensitivity to tetracycline (88.5%), nitrofurantoin (96.3%), and imipenem (100%), respectively.

Conclusion

This study indicated a high prevalence of UTIs (56.7%) in pregnant women, though most of them showed no clinical manifestation.
Histologic Characterization of Histoplasmomas
Authors: Demkowicz Ryan , Procop Gary
Published: September 2019

Introduction

Histoplasmomas are often found incidentally in surgical specimens, but there are no clear reporting guidelines to describe the subtle differences in the stages of organization of the granuloma. This study establishes grading criteria to more clearly communicate the stage of organization and resolution of these lesions, with the hope that this information could inform clinical decisions.

Methods

For an 11-year period, all surgical pathology cases with histoplasmomas in the final diagnosis with slides available were included in the study. After confirmation that Histoplasma yeasts were present, the granulomas were graded as

follows

grade 1, active granulomas with or without necrosis with minimal to no fibrous rim formation; grade 2, minimal to moderate granulomatous inflammation remained associated with a well-developed fibrous rim; and grade 3, no granulomatous inflammation remained, and a well-developed fibrous rim was present. Calcification and necrosis were also noted. Histoplasma yeasts was semiquantified. One to five yeasts were characterized as rare, 6 to 10 as few, 11 to 50 as moderate, and >50 yeasts as many.

Results

Forty-two cases were included in the study. The lesions were graded as

follows

3 grade 1, 19 grade 2, and 20 grade 3 lesions. Calcifications increased with grade (grade 1: 0 [0%], grade 2: 10 [52.6%], grade 3: 18 [95%]). All histoplasmomas had necrosis. The number of yeasts detected, stratified by grade, was as

follows

grade 1, rare (1) and many (2); grade 2, rare (6), few (1), moderate (1), and many (11); and grade 3, rare (2), moderate (4), and many (14). None of the patients developed active histoplasmosis for the duration of their follow-up at our institution.

Conclusion

The proposed grading of histoplasmomas provides an indication to clinicians of the stage of activity or resolution of an excised histoplasmoma. These data do not support the use of antifungal therapy in patients with grade 2 or 3 histoplasmomas.
Incidence of Enteropathogenic Escherichia coli among Infants at Eleyele Comprehensive Health Centre, Ile-Ife, Osun State
Authors: Faseyi Kayode , Onifade Jaiyeola
Published: September 2019

Objectives

This work was carried out to find the incidence of enteropathogenic Escherichia coli in children below 5 years of age who complained of having diarrhea at Eleyele Comprehensive Health Centre, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife. The work was also done to determine the incidence in different age groups of both sexes.

Methods

All specimens were cultured as routinely done at the bacteriology laboratory in Obafemi Awolowo University Teaching Hospital for stool samples. Colonies of lactose fermenters were processed after overnight incubation at 37°C. Nonlactose fermenter colonies were discarded. Out of 200 colonies isolates on MacConkey agar, there were 150 lactose fermenters and these were all processed. The other 70, which were Gram-positive cocci, were discarded. These were subjected to biochemical examination such as treating them with sugars, for the production of acid and gas, indole production, motility with sugars, citrate utilization, Voges-Proskauer, and methyl red tests.

Results

Out of 150 strains examined, only 80 strains obeyed IMVic ++ -- reactions. These were serotyped to know the enteropathogenic strains. From the result obtained, 23 strains reacted positively with polyvalent antisera (polyvalent 2, 3, 4 antisera), of which 13 strains gave a positive reaction with corresponding monovalent antisera. There were five strains from polyvalent 2 antisera, five strains from polyvalent 3 antisera, and three strains from polyvalent 4 antisera. In close study of this work, total percentage of females with diarrhea was 44.5% while total percentage of males with diarrhea was 55.5%. Out of these 80, E coli was isolated, and from these, 13 enteropathogenic E strains were isolated (16.25%). Patient aged below 2 years gave nine strains (69.2%), aged 2 to 3 years gave two strains (15.4%), aged 3 to 4 years gave one strain (7.7%), and aged 4 to 5 years gave one strain (7.7%). Also, close examination of result revealed that male children had the greater percentage of enteropathogenic infection, with 8 strains out of the 13 strains serotyped (61.5%) and female children with 5 strains (38.5%).

Conclusion

E coli remains an important cause of infant diarrhea. Although epidemics of infant diarrhea caused by enteropathogenic E coli have almost disappeared from the developed countries, it is still very common in developing countries. The relative importance of enteropathogenic E coli as a cause of infant diarrhea needs to be reassessed and new diagnostic techniques will also help to simplify this task.