bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Grade Uterine Sarcoma with BCOR Internal Tandem Duplication Presenting With Total Uterine Inversion
Authors: Greenwell T J , Kumar S , Hysell C
Published: October 2020

Casestudy: High-grade uterine sarcomas are rare mesenchymal tumors in which the underlying genetics of many have been recently elucidated. BCOR internal tandem duplications are present in a subset of high-grade uterine sarcomas. We report a diagnostically challenging case of a high-grade uterine sarcoma with a BCOR internal tandem duplication presenting with total uterine inversion. The case is that of a 24 year old G0P0 female with a four month history of intermittent diffuse abdominal pain and abnormal uterine bleeding. Pelvic examination revealed a mass protruding to the hymenal ring. The patient was suspected of having a prolapsed fibroid through the cervix, and a myomectomy was planned. During the procedure, total uterine inversion was noted as a result of a submucosal mass emanating from the uterine apex. The mass was removed off a broad base using sharp dissection, and the uterus was reverted in a subsequent procedure. Grossly, the mass was polypoid, rubbery, and measured 7 cm in greatest dimension. It was grey-white to red-brown, variegated, and fibrotic with focal hemorrhagic areas.

Histologically, the neoplasm had variable cellularity with spindle cells and a myxoid background. There was diffuse mild to moderate cytologic atypia and areas of increased mitotic activity. Tongue-like growth was present at the interface of the tumor with the normal myometrium. The neoplastic cells showed strong immunoreactivity for cyclin D1, BCOR, and TRK. There was focal immunoreactivity for CD10, and ALK was negative. Next-generation sequencing was performed and demonstrated an insertion into the BCOR gene, consistent with a diagnosis of high- grade uterine sarcoma with BCOR internal tandem duplication. In conclusion, we report an interesting presentation of a high-grade uterine sarcoma with BCOR internal tandem duplication causing total uterine inversion. The morphologic features and immunohistochemical profile suggested the possibility of the entity, and next generation sequencing confirmed the diagnosis.
A Fatal Case of Pediatric Primary Myxoid Liposarcoma of the Orbit: A Rare Tumor in an Unusual Location Presenting with Widespread Metastasis
Authors: Baqir A , Xie Q
Published: October 2020

Introduction/Objective

A liposarcoma is a tumor derived from primitive mesenchymal cells undergoing adipose differentiation. Liposarcomas are uncommon in childhood, representing only about 2% of childhood sarcomas. Among liposarcomas, is a very rare subtype, the so-called ‘pleomorphic myxoid liposarcoma’ which has extensive myxoid changes and scattered pleomorphic cells. Here we report an autopsy case of an extensively metastatic pleomorphic myxoid liposarcoma.

Methods

A 12 year-old, African-American boy presented in the ED with ascites and shortness of breath, who later expired despite resuscitation. Autopsy finding showed a primary lesion in the left superior orbital fissure with diffuse metastasis to liver, replacing most of the liver parenchyma (liver weigh 8500 g). Metastatic foci are also present in gallbladder, pancreas, large intestine, bilateral lungs, and inner and outer surfaces of cranium. Histologically, tumor at all sites shows similar morphology, revealing scattered pleomorphic lipoblasts and a myxoid background with arborizing vasculature. Lipoblasts show indented and distorted nuclei and cytoplasmic vacuoles.

Immunohistochemically the tumor cells are immunoreactive for p16 (diffusely and strongly) (Figure, D) and S100 (weakly) and negative for AE1/AE3, myogenin, synaptophysin, GFAP, EMA, and CD34. FISH was negative for MDM2 and t(12;16)(q13;p11.2) FUS-DDIT3 rearrangement, ruling out conventional myxoid liposarcoma.

Conclusion

This case shows the aggressive nature of a poorly studied entity in an uncommon age group and emphasize the need to study childhood liposarcomas in more detail.
Evaluation Of The Carcinoembryonic Antigen Test In Patients With Resected Colon Cancer
Authors: Kamel Y S , Lotfy A
Published: October 2020

Introduction/Objective

To determine the effectiveness of carcinoembryonic antigen (CEA) in patient with known residual disease after resection of colonic cancer

Methods

Serial carcinoembryonic antigen (CEA) levels were measured in 43 patients following incomplete excision of colorectal cancer. Twenty-seven patients received chemotherapy. The patients reported in this study were amongst those participating in a randomized trial of chemotherapy following palliative resection of colorectal cancer. All patients had a resection of colorectal cancer leaving behind macroscopic quantities of tumour, though of a small total residual bulk. The residual sites of tumour were recorded as: (a) local - where there was local extension of the tumour; (b) nodal - where there were clinically involved nodes remaining, with histological confirmation of involved nodes in the resected specimen; (c) hepatic - where small hepatic metastases were noted, individually not greater than 2 cm in diameter and in total representing less than 10% of the liver bulk; (d) peritoneal - where peritoneal tumour seedlings remained, with histological confirmation of at least one of the seedlings.

Results

Of the 43 patients studied after operation and prior to chemotherapy, the mean log CEA was 1.19 and only 3 patients exceeded 1.48, despite the fact that all patients were known to have residual tumour. Similarly, the mean log CEA at 3 months for the total group remained at 1.26 but 6 patients now had abnormal values. Thereafter the mean values of the total group exceeded the upper limit of normality and increasing numbers of patients showed elevated CEA values. About one half of the patients had levels of CEA well within the normal range during the first postoperative year despite the evidence of residual disease documented at operation.

Conclusion

The most appropriate application for a marker such as CEA may be as an assessment of the effect of chemotherapy in patients who have a definite, but objectively unmeasurable, tumour load.
The Detection by Immunofixation Electrophoresis (IFE) of Monoclonal Proteins in Veteran Patients with Hypogammaglobulinemia on Negative Serum Protein Electrophoresis, the Veteran Affairs Medical Center (VAMC) Experience
Authors: Petersen J M , Litman M , Millili R , Jhala D
Published: October 2020

Introduction/Objective

Serum protein electrophoresis (SPEP) is the backbone laboratory test for the detection of abnormal monoclonal proteins. However, IFE is a sensitive assay that can sometimes detect monoclonal proteins even when the corresponding SPEP is negative. The fact that IFE is more sensitive than SPEP combined with the need to avoid overutilization of IFE has led to published algorithms for guidance. Hypogammaglobulinemia in a new patient has been recognized in these algorithms as a reason to reflex to IFE when SPEP is negative, though studies on veteran patients are sparse. Therefore, this QA study of the percentage of positive IFEs in negative new SPEP veteran patients with hypogammaglobulinemia was undertaken to ensure reflex IFEs would still be indicated.

Methods

As part of a quality assurance/quality improvement project, a retrospective Vista/Fileman search of all SPEPs with IFE performed from January 2017 to February 2019 was undertaken to identify cases of SPEPs showing hypogammaglobulinemia (<0.7 g/dL). Diagnostic comments were then analyzed to identify cases of hypogammaglobulinemia along with the M-spike (<0.1 g/dL) to identify negative SPEPs. Only those cases that were consistent with first time hypogammaglobulinemia without an obvious M-spike were included and tabulated for calculations. Any result that was not negative for a monoclonal band was considered as positive.

Results

There were a total of 194 specimens that met the criteria of SPEP with hypogammaglobulinemia and standard comments consistent with first time analysis and without an obvious M-spike on SPEP. Out of these 194 specimens, 45 had a positive result, either as a monoclonal band comigrating with the beta protein peak or as a very faint gamma or beta monoclonal band. This represented approximately 23% of the specimens, about double the literature published rate for the non-veteran population.

Conclusion

The performance of IFE on new hypogammaglobulinemia veteran patients appears to be indicated like previously published algorithms and is supported by the fact that about double (23%), compared to the non-veteran population, had positive IFEs despite negative SPEPs. IFE is a helpful tool for new hypogammaglobulinemia patients for the detection of monoclonal proteins despite negative SPEPs.
Cytology-Histology Correlation of Hydatid Cyst: A Case Study and Literature Review
Authors: Agarwal A , Rosca O , Mody K , Mukherjee I
Published: October 2020

Casestudy: Hydatid cyst results when humans get infected by ingesting the eggs of Echinococcus Granulosus. Upon release, the six-hooked oncospheres penetrate the intestinal wall and migrate via circulation to various organs, mostly liver and lung. Here, they develop into hydatid cyst. The cyst enlarges gradually and is filled with daughter cysts and protoscolices.

We report the case of a 69-year old female, native of Uzbekistan, who presented with right upper quadrant pain. Imaging showed a 20 cm liver cyst and multiple pelvic cysts with a stage of CE2 implying that they were most likely functional. Serum Echinococcal antibody was positive. After 2 months of Albendazole treatment, there was no radiological change. The patient underwent laparoscopic puncture aspiration and injection with 20% saline (PAIR) and pericystectomy of the pelvic cysts. The aspirate revealed scattered scolices, inflammatory cells and abundant amorphous debris consistent with hydatid cyst. Bilateral 5-cm pelvic cysts had pale yellow, soft to firm walled, multiple cavities. Microscopy revealed a fibrofatty outermost layer with chronic inflammation and a two-layered cyst wall including a thin germinal epithelium covered by a thick acellular outer membrane. Multiple parasites, some degenerate (dense eosinophilic) were present, confirming the cytologic diagnosis of cystic echinococcosis. Following further treatment with Albendazole, she underwent a robotic assisted PAIR and partial peri-cystectomy of the liver cyst with repair of the duct to cyst communication. The liver cyst contained daughter cysts of Echinococcus and brood capsule with protoscolices. After 2 months more of Albendazole her Elisa was intermediate.

A prior study reported cytopathologic diagnosis of hydatid cyst in 17 patients evaluated for various masses. Our case highlights the role of cytology sampling in confirming the diagnosis of hydatid disease. Potentially fatal in untreated patients, this entity has to be considered in the differential diagnosis of cystic lesions.
Quality and Patient Safety in a Pathology Residency Training Program
Authors: Demkowicz R , Sapatnekar S , Chute D
Published: October 2020

Introduction/Objective

Since the start of the new millennium, optimization of Quality and Patient Safety (QPS) has taken a renewed focus in the healthcare industry. Consequently, the Accreditation Council for Graduate Medical Education has mandated that QPS be a part of residency training. We have previously presented our curriculum designed to meet the specific needs of Pathology training programs, and covering four content areas: Handoffs, Error Management, Laboratory Administration, and Process Improvement. We are now presenting implementation.

Methods

To implement this curriculum, we 1) created online modules for self-directed learning on basic topics (using courses developed by IHI and CAP, and assigned articles), and paired these with faculty-facilitated interactive learning activities on more complex topics, including proficiency testing, root cause analysis and test utilization, 2) assigned every resident to a QPS project that was aligned with departmental priorities, led by a faculty advisor, and ran over 8- 10 months, and 3) appointed a QPS Chief Resident to coordinate and support the residents’ QPS activities. We measured the impact of the curriculum by comparing RISE laboratory accreditation percentiles and QPS curriculum quiz scores before and after curriculum implementation.

Results

After its implementation, RISE percentiles increased by at least 25 for every PGY, and QPS quiz scores increased by at least 10% for 3 of 4 PGY. Every QPS project was presented at Grand Rounds, and 4 were presented externally, including 2 at national conferences.

Conclusion

Our curriculum was successful in improving residents’ knowledge and competence in QPS. Challenges included designing appropriate learning activities, tracking completion of activities, coordinating faculty schedules and maintaining resident buy-in to the curriculum. We believe that the basic structure of our curriculum offers a solid foundation to which revisions can be made as QPS priorities evolve, and which can be readily adapted to other programs and locations.
Building Entrustable Professional Activities In Residency Training: Peripheral Blood Smear And Body Fluid Analysis
Authors: Theil K S , Nakashima M O , Ondrejka S L , Cotta C V
Published: October 2020

Introduction/Objective

Entrustable professional activities (EPAs) are defined as specialty-specific tasks representing a unit of professional practice that can be entrusted to unsupervised performance by a trainee following attainment of sufficient task-specific competence. EPAs and periodic competency assessments also provide a framework for evaluating relevant ACGME milestones. We describe our experience creating EPAs for peripheral blood smear (PBS) and body fluid (BF) analysis through which residents became qualified to act as laboratory testing personnel.

Methods

Training occurred during a 6 week “boot camp” for PGY2 and PGY4 residents in July-August 2018 and July-August 2019. Training for PBS included didactic lectures in automated hematology and RBC morphology (2 hr) and WBC and platelet morphology (2 hr); faculty-guided microscope reviews of RBC (2 hr) and WBC morphology (2 hr) using a training checklist; completion of RBC and WBC self-assessment quizzes; and a 40 question graded exam that covered cell identification, lab protocols, and case scenarios. Training for BF included didactic lectures (2 hr); faculty-guided microscope review of BF slides using a training checklist; completion of a BF self-assessment quiz; and a 40 question graded exam that covered cell identification, lab protocol, and case scenarios. Following successful completion of the graded exam residents were deemed competent to perform unsupervised review of cases initially flagged as abnormal by laboratory technologists; they were required to obtain attending review prior to release of results in defined situations. Formal competency assessments according to CLIA standards were done at 6 and 12 months after initial training. Impact on laboratory workflow and turnaround time was assessed before and after training.

Conclusion

We successfully created EPAs for PBS and BF analysis through which residents became qualified to act as laboratory testing personnel. There was no adverse impact on laboratory turnaroud time, and the number of PBS and BF cases requiring attending pathologist review decreased. Residents appreciated this tangible opportunity to gain graduated responsibility that prepared them for future practice. Periodic competency assessments provide an opportunity to evaluate relevant ACGME milestones. Our training and assessment program and EPAs can serve as a template for other residency programs.
Evaluation Of Some Markers Of Haemolysis – Endothelial Dysfunction And Haematological Parameters In People With Sickle Cell Disease Leg Ulcers
Authors: Otokiti O E , Bassey G M
Published: October 2020

Introduction/Objective

Sickle cell leg ulcer (SCLU) is one of the commonest cutaneous manifestation of the sickle cell anaemia (SCA). This study was designed to evaluate the haematological parameters and contribution of haemolysis to leg ulcers in persons with sickle cell anaemia

Methods

A comparative cross-sectional study of 73 participants (24 sickle cell leg ulcer-SCLU, 24 sickle cell without leg ulcer-SCWLU and 25 healthy controls). Physical examination was conducted to grade the SCLU. ELISA kits were used to analyse Nitric oxide, while FBC, Reticulocyte count, liver function test (AST and ALT), total Bilirubin (unconjugated and conjugated) were determined using standard methods. ANOVA was used to compare the association between sickle cell leg ulcers and markers of haemolysis-endothelial dysfunction among the three groups. Probability score of less than 5% (p-values<0.05) was considered statistically significant

Results

There was no statistically significant difference in the age distribution of the participants in this study. Those with SCLU were diagnosed at an older age and majority (52.2%) had clinical stage 2 leg ulcer. Among the markers for haemolysis-endothelial dysfunction (HED); Reticulocyte production index (PRI) was lower in SCLU (1.87 + 0.72) compared to SCWLU, (2.04 + 0.78) p= 0.01. Total and unconjugated bilirubin (µmol/L) level was higher for SCLU (53.0 + 17) in comparison to SCWLU (42.2 + 8.2) with statistical significance of p=0.00. Aspartate and alanine transaminases (AST and ALT) (U/L) were higher in SCLU in comparison with SCWLU, (60.1 + 21.5, 43.8 + 15.8 and 30.1 + 13, 29.8 + 11.7) respectively, and was statistically significant p= 0.00. However Nitric oxide was not statistically different between SCLU and SCWLU mean ± SD (49.57 + 12 and 46.19 + 9) respectively. p = 0.35

Conclusion

Markers of haemolysis were higher in participants with sickle cell leg ulcer (SCLU) when compared to those without leg ulcer (SCWLU). However, no statistically significant difference was obtained for Nitric oxide (NO) between the two groups. Therefore, markers of haemolysis cannot be used as an effective predictor for risk of developing SCLU but early diagnosis of SCA can prevent SCLU.
A Rare Case Of Kikuchi-Fujimoto Disease Displaying Chromosomal Abnormality
Authors: Zhang Y , Ding L , Aftab L , Rushton P
Published: October 2020

Introduction/Objective

Histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease (KFD), is a rare and benign self-limiting process primarily affecting 20~35-year-old Asian women with spontaneous remission after weeks to months of illness. Although the involvement of T cell-mediated immune response, infections, and HLA class II gene have been proposed as possible etiologies, the detailed pathogenesis has not been elucidated. Very few literatures exhibited KFD displaying chromosomal abnormality such as t(2:16).

Methods

Here, we report a rare case of KFD with novel karyotype abnormalities in a 24-year-old African American male. It presented as painless cervical lymphadenopathy for one month without fever, night sweats, or weight loss. An excisional biopsy of the lymph node (LN) was performed.

Results

Tissue culture for bacteria and flow cytometry of the LN were negative. Histopathology revealed numerous pale circumscribed foci composed of lymphocytes, histiocytes, plasmacytoid dendritic cells, and abundant karyorrhectic debris in the background of coagulative necrosis. No neutrophils or hematoxylin bodies are seen.

Immunohistochemical studies showed CD3+/CD4+ T lymphocytes, CD68+ histiocytes, and CD123+ plasmacytoid dendritic cells. Abnormal karyotype was observed as: 46, XY, del(6) (q?16q?22).

Conclusion

We present this case to demonstrate that 1. Although KFD is most prevalent in young Asian females, it may occur in both genders and other ethnical groups and perhaps represents an underdiagnosed process. 2. KFD can mimic a variety of diseases such as rheumatologic, infectious, and hematologic malignancies; a thorough workup including serology, culture, and flow cytometry is needed to exclude serious diseases such as systemic lupus erythematosus and malignancy to render an early diagnosis which may avoid unnecessary diagnostic and therapeutic interventions. 3. Cytogenic abnormalities, although observed in many malignancies, should not be used as a sole determinant of malignancy, and the interpretation needs to be in a relevant clinical and histopathological context in a multidisciplinary setting to avoid misdiagnosis and inappropriate treatment.
Discordant Lymphoma: A Sequential Case of Burkitt Lymphoma and Classic Hodgkin Lymphoma
Authors: Mai B , Berumen A , Herrmann A , Chen L
Published: October 2020

Casestudy

A discordant lymphoma is a rare condition in which two or more subtypes of lymphomas can occur in different anatomic sites; the distinct sub-classifications can present concurrently or sequentially. We present a rare case of a second primary Classic Hodgkin Lymphoma (CHL) several years after achieving remission from an unusual presentation of a non-Hodgkin lymphoma (NHL).

Results

A 40-year-old HIV-positive male presented to the emergency department for acute cholecystitis. Sections of his gallbladder revealed atypical monomorphic lymphocyte infiltrate that were diffusely positive for CD10, CD20, BCL6, and PAX5, and negative for BCL2, CD5, Cyclin D1, and MUM1. The proliferation index by Ki-67 was 100%.

EBER ISH is positive. A FISH assay for the C-MYC break apart probe and dual fusion of IgH and BCL2 showed a rearrangement of 8q24, highly suspicions for a 8;14 translocation, classically seen in Burkitt Lymphoma (BL).

Subsequently, he was placed on RA-DA-EPOCH and achieved remission.

Seven years later, he presented with nausea, vomiting, headaches, and blurry vision. An excisional biopsy of his right cervical lymph node was performed. The histological sections showed effaced nodal architecture with sclerotic fibrosis and necrosis. There were scattered Hodgkin cells/Reed-Sternberg (HRS) cells in the background of lymphocytes, plasma cells, histiocytes, and eosinophils. The HRS cells were positive for CD15, CD20 (weak), CD30, BCL6, MUM1, and PAX5 (weak), and negative for ALK, CD10, and CD45. EBER ISH was positive and HHV8 was negative. These features were consistent with a CHL, nodular sclerosis subtype.

Conclusion

Malignancies in HIV patients pose a unique challenge as they often possess distinct characteristics distinct, including unique aspects of tumor localization, atypical pathological features, unusual growth behavior, and advanced stage at presentation. Epstein-Barr virus (EBV) is strongly linked with several HIV-associated lymphomas, as it encodes several proteins including LMP-1, LMP-2A, BHRF-1, EBNA-3A, and EBNA-3C that are implicated in the development of NHLs. The identification of discordant lymphomas may have variable prognoses and different treatment modalities. In addition, the study of such discordant lymphoma cases may provide more insight on the etiology and inter-relationship of clonal evolution in lymphoma.
The Outcome Of Preoperative Transfusion Guideline On Sickle Cell Disease Patients At King Fahd Hospital-Jeddah (Ksa)
Authors: Felemban S M
Published: October 2020

Introduction/Objective

We have developed a local hospital transfusion guidelines to reduce and prevent the perioperative and the postoperative complications. This study was conducted to evaluate the outcome of practice for preoperative transfusion therapy in SCD patients in our institution.

Methods

A retrospective review of SCD patients undergoing surgery at King Fahd Hospital, Jeddah, Saudi Arabia was conducted between April 2005 and May 2010. The medical records were reviewed to define the perioperative risks and the postoperative complications in relation to the type of transfusion modality selected.

Results

The medical record of 75 sickle cell disease patients in whom the hematologists were consulted for their preoperative assessment. Preoperatively, 25.3 % had complete exchange transfusion (CETX), 17.3 % had partial exchange transfusion (PETX), 26.7 % had simple top up transfusion (STX) and 30.7 % had no transfusion (NTX). The postoperative complications were 20% vaso-occlusive crises (VOC), 2.7% acute chest syndrome (ACS), and 16% had fever. The mean duration for the hospital stay was 7.36 with SD of 5.83. There was no significant difference in the outcome between all types of transfusion modalities, the P value was (p 0.245), (p 0.282), (p 0.133), (p 0.220) for postoperative fever, VOC, ACS, and the length of hospital stay, respectively. However, The correlation was highly significant between the post-transfusion haemoglobin (Hb) level and the occurrence of postoperative fever (p 0.01) and VOC (p 0.03).

Interestingly, SCD patients who received hydroxyurea were observed to have less postoperative complication like fever, and the result was highly significant (P<0.01), while those who received prophylactic heparin in the postoperative period were found to have a reduced length of hospital stay (p<0.01) and vaso-occlusive crises (p <0.01).

Conclusion

The guidelines for preoperative transfusion in SCD patients was effective in reducing the postoperative morbidity and mortality. However, the selection of the optimum regimen for different surgical types in sickle cell disease patients and the surgical situations where preoperative transfusion is needed were all established in this guidelines.
Targeting Mediators Of Chronic Inflammation: A Promising Alternative Therapeutic Use Of Plant-Derived Remedies With Potent Bioactivity And Lower Cytotoxicity
Authors: Adebayo S
Published: October 2020

Introduction/Objective

Medicinal plants have a long history of use and has been exploited for basic health care needs for many centuries. The various parts of plants are rich sources of a plethora of pharmacologically active remedies that has remained largely unexplored for their therapeutic capabilities. Grewia mollis is one of the medicinal plants that are used to treat painful inflammatory conditions including rheumatism and associated fever. The inhibition of enzymes involved in prostaglandin (PG) synthesis are of great interest in combating chronic inflammation. Cyclooxygenases (COX) and Lipoxygenases (LOX), in particular COX-2 and 5-LOX utilize different pathways for PG synthesis and are important drivers of chronic inflammation. However, the use of conventional anti-inflammatory drugs and specific enzyme inhibitors against them are associated with severe adverse side-effects and organ toxicities.

Therefore, attention has shifted to the search for potent and safer alternative strategies to treat chronic inflammation involving these mediators

Methods

The leaf part of G. mollis was extracted with solvents of varying polarities. The extracts were tested in vitro against COX-1, 2 and 5-LOX. In addition, the cytotoxicity and selectivity index of the plant extracts were evaluated using vero monkey kidney cells

Results

The hexane fraction of G. mollis leaf extracts had better inhibition against COX-1 (0,97±1,9 µg/mL) and COX-2 (1,13±0,2 µg/mL) when compared with the indomethacin control (1,30±0,6 µg/mL) and (1,52±0,2 µg/mL) respectively. Also, the butanol fraction inhibited 5-LOX (12,48±2,9 µg/mL) better than quercetin positive control (61,82±5,5 µg/mL). Overall, the extracts and fractions indicated reduced cytotoxicity (30,56-689,39 µg/mL) relative to the doxorubicin control (2,59 µg/mL).

Conclusion

The results indicated that extracts of G. mollis contained bioactive molecules capable of inhibiting the activities of C0X and 5-LOX with lower cytotoxicity. Pharmacologically active molecules with safety profile could be used, at least as a part of the template for remedies against mediators of chronic inflammation
Serology Curriculum For Residents Using Online, Case-Based Simulation Modules
Authors: Dent E A , Guarner J
Published: October 2020

Introduction/Objective

Although serology concepts are a frequent exam topic for Pathology trainees, serology education remains challenging, in part, because serologic test performance occurs in different laboratories (immunology, microbiology, or chemistry.) Serology education topics may be eclipsed by larger concerns of the laboratory where serology resides. To evaluate the utility and advantages of online modules as adjuncts to other education modalities used during a standalone serology rotation, we developed a one-week curriculum in which residents were given four case-based vignettes to discuss with faculty, eight online case-based simulation modules, and bench time in the laboratory performing serological tests (RPR, VDRL, hepatitis, and HIV).

Methods

The online modules are housed within an e-learning portal. Residents were asked to print certificate of completion for eight assigned modules. Residents were offered an anonymous survey of the rotation between one week and up to 2 months after completing the rotation.

Results

Twenty-three first-year residents (spanning a 3-year period) completed the online modules, and 10 (43.5%) completed the survey. The average percentage of correct answers ranged from 73% for the HIV module to 88% for the hepatitis B module. The number of residents with scores below 80% was highest for EBV and Cryptococcus modules (8 and 9 scoring <80% respectively) and lowest for hepatitis B and toxoplasmosis modules (2 and 3 respectively). On the survey, residents stated they had repeated the online modules between 1 and 4 times, averaging between 1 and 2 attempts. Although there was no specific module rated as most enjoyable, the toxoplasmosis and EBV modules were picked by 3 out of 10 residents as his or her favorite. There was no consensus on which module was subjectively easiest or most difficult, nor which was least enjoyed. The majority of the residents (7/10) found the modules helpful and all ten residents stated that they “learned more” after completion of the modules because they reinforced (6/10) concepts important to serologic testing.

Conclusion

The online, case-based simulation modules are effective additions to a serology curriculum that includes case-based discussions and time in the laboratory performing tests. The online modules are effective because they provide additional structure and reinforce learning within the serology curriculum.
False Negative Rate (2%) of Lynch Syndrome Screening Utilizing A Two-Antibody (PMS2/MSH6) Immunohistochemistry Panel: Failure To Detect a Subset of MSH2-Deficient Endometrial Carcinomas
Authors: Wood R , Murray S , Offman S , Carter M
Published: October 2020

Introduction/Objective

Lynch syndrome (LS) is an inherited condition caused by defective DNA mismatch repair (MMR), leading to a higher incidence of cancers of multiple sites. Screening for LS is now recommended for new diagnoses of endometrial cancer (EC) using either two- (PMS2, MSH6) or four-antibody (2/4Ab) (PMS2, MSH6, MSH2, MLH1) immunohistochemical (IHC) panels. The 2Ab panel assumes consistent loss of expression of the minor dimer component, PMS2 or MSH6, when the major component, MLH1 or MSH2, respectively, is lost due to mutation. Recent studies have indicated that 2Ab testing may lead to underdiagnosis of MSH2-deficient tumors in cases where MSH6 staining is weak or focal, potentially leading to underdiagnosis of LS.

Methods

We conducted a retrospective study using archived slides for 293 cases of EC (identified via LIS search from 2016-2019) that were screened using the 2Ab panel (expanded to 4Ab when PMS2 or MSH6 were negative). MSH6 expression was reviewed; if weak, focal (less than 10% staining), or both, MSH2 IHC was performed. When a previously undetected loss of MSH2 expression was found, the attending clinician was informed such that referral to medical genetics could be arranged.

Results

Results Overall, 68 (23.2%) tumors were MMR deficient, with 54 (18.4%) showing MLH1/PMS2 loss, 7 (2.4%) with MSH2/MSH6 loss, 2 (0.7%) with isolated PMS2 loss, 4 (1.4%) with isolated MSH6 loss, and 6 (2.0%) with isolated MSH2 loss (i.e. intact but weak/focal MSH6, seen in biopsy and hysterectomy specimens). Interestingly, 1 tumor (1.5%) demonstrated loss of MSH6, MLH1 and PMS2. Two tumors (0.7%) with isolated MSH2 loss were previously unrecognized as MMR-deficient and hence at high risk for LS. Both cases were evaluated by PCR for microsatellite instability (MSI) and confirmed to have high-degree MSI.

Conclusion

This study identifies the frequency of mismatch repair deficient endometrial cancers in Atlantic Canada, highlights a potential pitfall of using two-stain IHC screening for Lynch syndrome, and supports emerging recommendations for universal Lynch syndrome screening in EC.
Human BK Polyomavirus Nephropathy (BKVN) In Non- Kidney-Transplant Patients
Authors: Chen Wongworawat Y , Zuppan C
Published: October 2020

Introduction/Objective

Human BK polyomavirus nephropathy (BKVN) occurs in up to 10% of renal transplant recipients, and can result in graft loss. Transplant biopsy is the gold standard to diagnose BKVN, and SV40 immunohistochemical (IHC) staining is helpful in confirming the diagnosis. BKVN is uncommon outside the setting of renal transplantation. To understand more about its occurrence in other contexts, we reviewed our renal biopsies files for cases of BKVN.

Methods

Our renal biopsy files for the past 20 years were reviewed for all cases with a diagnosis of BKVN or polyoma virus infection, and the clinical characteristics of the affected patients noted.

Results

Evidence of BKVN was found in 44 renal biopsies, of which 39 (86%) were renal transplant patients. Of the remaining five patients (14%), two had undergone heart transplantation, one lung transplantation, one was undergoing chemotherapy for acute lymphoblastic leukemia, and one patient had active HIV infection. All patients had elevated serum creatinine, and four out of five patients had documented BK viremia. Four of the five biopsies showed typical tubular injury with viral nuclear cytopathic changes (inclusions). In the lung transplant patient, the biopsy showed advanced chronic tubulointerstitial injury without distinct viral inclusions, but SV40 staining confirmed the presence of BK virus antigen.

Conclusion

The BKVN is distinctly uncommon outside the context of kidney transplantation. In our series, 14% of patients with BKVN were not kidney transplant recipients, but all were immune compromised in some fashion. The pathologic features of BKVN appear similar, regardless of whether the host is a renal transplant recipient or not.

Although uncommon, it is important to consider the possibility of BKVN in non-renal transplant patients with persistent or progressive renal dysfunction.
Scopes and Challenges In Educating The Clinical And Nursing Staffs Regarding The COVID -19 Specimen Collection And Processing For Testing In The Municipal Public Health System Based Ambulatory Care Health Clinics In New York City
Authors: Huq Ronny F M
Published: October 2020

Introduction/Objective

With the emergence of Novel COVID-19 infection in the New York City, at the initial phase a very limited information and guidelines were available from the federal and state health authorities and only state lab could provide the COVID -19 testing. Sparsity of the authentic information and up surging of the misinformation in the social media and rapidly evolving different reference testing laboratories were creating confusions and challenges among our clinic providers and nursing staffs. With periodic incorporation of updates on standardized protocol and guidelines, we formulated a plan and delivered that in a coordinated manner in educating the clinical and nursing staffs regarding the COVID -19 specimen collection and processing for testing to overcome that.

Methods

We gathered all the communications for COVID -19 from the federal, state and city health authorities and our corporate management about the testing methods, collection and processing requirements and specimen pickups. We verified and customized that information, prepared and circulated them in detailed PowerPoint presentation and then updated that periodically with any addition or changes in the testing reference labs and/or their specimen requirements.

Results

With periodic, standardized and updated guidelines and detailed verified information and instructions for sample processing, a uniform and much coordinated specimen collection and processing could be achieved and all of our five-borough spanning multisite municipal ambulatory clinics could collect and process the COVID-19 specimens properly.

Conclusion

Centralized, Planned and concerted education planning and timely delivering that to the clinical and nursing staffs could tremendously help in answering many relevant queries and curtailing confusion and properly collecting and handling the specimens in emerging infection like COVID-19 in a large city municipal ambulatory care health system.
Genotyping of the Galactosemia GALT 591 A>G Mutation by Pyrosequencing
Authors: Bamford J B , Ramirez J M , Prewit W A , Robinson W J , Bennett K M
Published: October 2020

Introduction/Objective

This project aimed to design a pyrosequencing assay capable of genetically analyzing the presence of GALT 591 A>G mutation for the diagnosis of galactosemia. Galactosemia is an autosomal recessive disorder that affects enzyme activity of galactose-1-phosphate uridylytransferase (GALT). This enzyme is responsible for proper processing of galactose to glucose; if not broken down the accumulation of galactose in the body results in developmental delays, clouding of the eyes, speech difficulties, and intellectual disabilities. Pyrosequencing offers a valuable platform in assessing whether patients are wild type unaffected (A:A), heterozygous carrier (A:G), or homozygous affected (G:G) at the alleles within the GALT 591 locus by measuring percentage of the wild type A allele and the mutant G allele.

Methods

PCR primers were designed for the mutation locus, and PCR amplification was optimized for the target 77 bp product, with verification by gel electrophoresis. The pyrosequencing assay was designed and validated on the Qiagen PyroMark Q24 instrument. Control samples included commercially purchased DNA from the Coriell Cell Repository.

Results

One hundred and thirty-three reactions were utilized to establish the following assay validation parameters: accuracy (100% for G:G, 95% for A:G and A:A), precision (determined by mean and standard deviation with a standard deviation of 0.6 for G:G, 4.55 for A:G and 4.85 for A:A), and limit of detection (10 ng DNA pre-PCR and 2 µL of PCR product loaded). Twenty-six blinded samples were utilized to test assay clinical performance, as compared against a high resolution melt curve assay.

Conclusion

It was determined that detection of GALT 591 A>G via pyrosequencing is highly sensitive and specific with a clinical sensitivity of 100% and a clinical specificity of 95.83%. It was concluded that this assay could be applied in a clinical environment for GALT 591 A>G genotyping to aid in galactosemia diagnosis.
Rat-Bite Fever: Updated Recommendations For Culture And Isolation Of Streptobacillus Moniliformis Using An Automated Continuous Blood Culture Instrument In A Clinical Setting
Authors: Szewc A M , Bell M E , Kelly A J , McQuiston J R
Published: October 2020

Introduction/Objective

Rat-bite fever and Haverhill fever are difficult to diagnose in a clinical setting due mostly to clinicians and laboratory professionals being unable to culture the causative agent-Streptobacillus moniliformis. SPS in blood culture bottles has historically been implicated as the complicating factor.

Methods

Utilizing the BDFX40 automated continuous blood culture bottle system and novel quantitative PCR data, we present how blood volume is critical in order to consistently detect, isolate and grow the organism in the presence of SPS using modern laboratory instrumentation in a clinical setting.

Results

We demonstrate here that 10ml of blood was determined to provide optimal results for detection and growth of S. moniliformis in 0.05% SPS. For all isolates tested, 100% (n=56) were detected or alerted as positive by the instrument, with the longest time required for detection being 102 hours (n=1) and the fastest time to detection being recorded at 13.4 hours. (n=1) with an average time of 26.5 hours (n=56).

Conclusion

During the course of this study, we determined that blood inoculum volume played a significant role in organism growth and detection. We found that in 100% of the isolates tested (and all the variations of testing within), SPS (up to a concentration of 0.05% w/v) in blood culture media appeared to be counteracted, allowing for the growth detection and culturing of S. moniliformis using an automated continuous blood culture system when 10ml of blood was used as an inoculum. This is the first study to report and suggest that a specific blood volume is critical when utilizing a closed commercial blood culture system to detect S. moniliformis, this research is the largest study of Streptobacillus moniliformis isolates to date.
Incidence Of Enteropathogenic Escherichia Coli Among Infants At Eleyele Comprehensive Health Centre, Ile-Ife
Authors: Faseyi K T
Published: October 2020

Introduction/Objective

This work was carried out to find the incidence of enteropathogenic Escherichia Coli in children below five years of age who complained of having diarrhea at Eleyele Comprehensive Health Centre, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife.

Methods

All specimen were cultured as routinely done in Bacteriology Laboratory in Obafemi Awolowo University Teaching Hospital for stool samples. Colonies of lactose fermenters were processed after overnight incubation at 37°c. Non lactose fermenter colonies were discarded. Out of 200 colonies isolates on MacConkey Agar, there were 150 lactose fermenters and these were all processed. Biochemical examination on sugars, for the production of acid and gas, indole production, motility, citrate utilization, voges-prokauer and Methyl red tests.

Results

Out of 150 strains, 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) out of which 13 strains gave a positive reaction with corresponding monovalent antisera. 5 strains from polyvalent 2 antisera, 5 strains from polyvalent 3 antisera, and 3 strains from polyvalent 4 antisera. In close study of this work, total percentage of female with Diarrhea cases were 44.5% total percentage of male with diarrhea cases were 55.5%. Out of these 80, Escherichia coli were isolated, from these 13 enteropathogenic Escherichia coli strains were isolated (16.25%). Patient with age group below 2 years gave 9 strains 69.2%, 2-3 years gave 2 strains (15.4%), 3-4 years gave 1 strain (7.7%) and 4-5 years gave 1 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

Escherichia coli remain an important cause of infant diarrhea. Although epidemics of infant diarrhea caused by enteropathogenic Escherichia coli have almost disappeared from the developed countries, it is still very common in developing countries. The relative importance of enteropathogenic Escherichia coli as a cause of infant diarrhea need to be reassessed and new diagnostic techniques will also help to simplify this task.
Cerebral Phaeohyphomycosis Due to Cladophialophora Bantiana in a Kidney Transplant Patient
Authors: Yu K , Devi P , Pulinthanathu R
Published: October 2020

Casestudy: Phaeohyphomycosis is a group of infections caused by pigmented, black, dematiaceous fungi and is responsible for cutaneous, superficial and deep mycoses, disseminated infection and brain abscesses. The primary agents involved include Alternaria spp., Exophiala spp. and Cladophialophora spp. Cerebral phaeohyphomycosis is particularly devastating with mortality rates as high as 70-80%. These fungi are becoming increasingly important opportunistic pathogens in solid organ transplant recipients (SOTR). We report a case of cerebral phaeohyphomycosis in a 65-year-old male with living donor kidney transplant for four years and has been maintained on immunosuppressive therapy with tacrolimus and prednisone. The patient presented with aphasia, frontal headache, loss of peripheral vision of right eye, and mental status change for three months due to several left- sided parieto-occipital brain abscesses. Left occipital abscess resection and parietal partial lobectomy were performed to reduce intracranial hypertension and to remove abscesses. Histopathological evaluation revealed brain abscess with pigmented fungal organisms with elongated, branched and septate. The pus aspirated during surgical excision of brain lesions grew black mold, identified as Cladophialophora bantiana. The patient’s neurological neurological condition had imporved after several weeks of combination antifungal therapy with posaconazole, liposomal amphotericin, and flucytosine. The lesions were initially suspected to be of tuberculous etiology, which was ruled out by histopathological examination. Such diagnostic dilemmas are common in the infection caused by Cladophialophora, which can cause treatment delay and death. Early diagnosis is therefore mandatory for the rapid treatment and survival of patients. As the number of SOTR increases, so does the incidence of fungal infections in that population. Surgery, along with antifungal therapy and a reduction in immunosuppression, are the cornerstones of treatment.
Incidental Prostate Infections: Developing the Prostate Microbiome
Authors: Daniel D , Zuretti A
Published: October 2020

Introduction/Objective

About 1 in 9 men will be diagnosed with prostate cancer in their lifetime. The traditional method of diagnosis is via a 12 core, trans-rectal biopsy. While this has been an appropriate method of investigation, a rectal approach to the prostate core made it difficult to differentiate prostatic bacterial infection from fecal contamination. Utilizing a sterile trans-perineal approach for biopsy, we were able to establish a true microbiome of the prostate, without contamination.

Methods

This is a prospective, IRB approved study. Men who were required to have prostate biopsies were offered a trans-perineal or trans rectal method of biopsy. Those who opted for trans-perineal biopsy with a negative urine culture met the inclusion criteria. Urine culture was performed prior to scheduling for the procedure. At time of biopsy, sterile cultures were taken from the rectum and one randomly selected prostate core. Cultures were grown for 5 days, and the results were recorded.

Results

Of the 93 patients who met inclusion criteria, eight men contained various bacteria within the sterilely accessed prostate core. Of the eight prostate cores which grew positive cultures, five of those patients had an isolated prostatic infection, without rectal or urinary co-infection. The most common infections included E. coli (n=2) and Klebsiella species (n=3).

Conclusion

New techniques in the performance of prostate biopsy provides the microbiology laboratory unique opportunities for investigation. This is the beginning of the study of the prostate microbiome, and future correlation with prostate cancer and isolated prostate infection are areas of future inquiry.