bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pirfenidone Alleviates Features of Well-Established Chronic Pancreatitis in Mouse Models
Authors: Palathingal Bava E , Tarique M , Iyer S , Sahay P , Dawra R , Saluja A , Dudeja V 
Published: October 2020

Abstract

Introduction/Objective
Chronic pancreatitis (CP) is a fibro-inflammatory disease of pancreas with no targeted therapy and is considered irreversible. Antifibrotic agent pirfenidone is FDA approved for idiopathic pulmonary fibrosis.
However, exact molecular mechanism of its action is not clear. The aim of this study was to evaluate pirfenidone as a therapeutic agent for CP.

Methods
Caerulein-CP was induced in C57BL/6 mice by caerulein injections (50ug/kgx7, i.p., hourly x twice weekly x10 weeks). At 11 weeks, animals were randomized and assigned to either saline or pirfenidone group (400 mg/kg/d by oral gavage for 5 weeks). Mice were euthanized at 17 weeks. L-arginine induced CP was induced by i.p. injections of L-arginine (4.5g/kg x2 hourly, once a week x 4) and treatment was started after 5 weeks of start. Mice were sacrificed at early time-points after starting treatment. Single-cell suspension of pancreata were used for flow- cytometry. Pancreatic atrophy, histology, fibrosis and cytokine mRNA profile were evaluated. In vitro studies were done on stellate cells.

Results
The treated caerulein-CP mice had improvement in pancreas/mouse weight ratio, (7.03±0.41 vs. 4.75±0.28; p&lt;0.0001). Histology scores and fibrosis markers were reduced. Pancreatic atrophy and histology scores showed significant improvement by day 14 of treatment in L-arginine CP. Flow cytometry showed that by day 7 of treatment there was significant reduction in macrophage infiltration (1.09 ± 0.18 % vs 3.26 ± 0.4 %; p&lt;0.001) and pro-fibrotic M2 macrophage markers [IL-4 (1.5 ± 0.1 % vs 2.8 ± 0.2%; p=0.007)], while M1 marker (MHC II) did not change. mRNA levels of pro-inflammatory and pro-fibrotic cytokines decreased, and of anti-inflammatory cytokines increased. In vitro study on stellate cells showed reduction in mRNA levels of pro-fibrotic and pro-inflammatory cytokines as well as fibrosis markers in treatment group.

Conclusion
Pirfenidone ameliorates well-established CP in mouse models by altering immune cells.
Vascular Pattern and Density in Clear Cell vs Clear Cell Papillary Renal Cell Carcinoma
Authors: Canete-Portillo S , Rodriguez Pena M , Wang D , Netto G J , Magi-Galluzzi C , Sanchez D F 
Published: October 2020

Abstract

Introduction/Objective
Renal cell carcinomas (RCCs) are well-vascularized tumors. Although clear cell RCC (ccRCC) shows a characteristic vascular network, in some cases may show overlapping features with other RCCs. Microvessel density (MVD) and architectural vascular arrangement in RCC have been characterized using CD31 and CD34 immunohistochemical (IHC) stains. To date, no studies have evaluated the vascular distribution in ccRCC compared to clear cell papillary RCC (ccpRCC). We aimed to identify potential differences in MVD, vascular pattern architecture and extent in ccRCC and ccpRCC.

Methods
Fifteen cases of ccRCC and 15 cases of ccpRCC were included in the study. ERG IHC stain and Bioquant Osteo 2019 Imaging Analysis Software were used to evaluate MVD in 12 cases (6 ccRCC, 6 ccpRCC). CD34 was used to evaluate architectural vascular pattern and its extent (% of tumor) in all cases. Mann–Whitney U test in STATA version 16.0 was used for statistical analysis.

Results
MVD means were 30.64 (CI: 17.9-43.29) in ccRCC and 29.2 (CI: 17.82-40.57) in ccpRCC. CD34 highlighted 4 distinct vascular patterns: lacunae, pseudoacinar, Golgi-like and scattered. The extent of patterns ranged from 0% to 90%. Heterogeneous distribution of different vascular patterns was found in both RCC groups. Although lacunae pattern was present in all RCC cases, pseudoacinar (100.0% vs 31.0%), Golgi-like (53.8% vs 100%) and scattered (53.8% vs 38.0%) patterns showed different distribution in ccRCC vs ccpRCC, respectively. Lacunae+pseudoacinar was the most frequent combination in all ccRCCs; lacunae+Golgi-like was identified in 77% of ccpRCCs. Pseudoacinar was the most extensive pattern in ccRCCs, meanwhile Golgi-like was the predominant pattern in ccpRCCs (p value&lt;0.05).

Conclusion
There was no difference in MVD between ccRCC and ccpRCC. However, the extent of vascular patterns pseudoacinar and Golgi-like was significantly different between ccRCC and ccpRCC. Distinct architectural vascular arrangement could help discriminate these entities.
Peripheral T-cell Lymphoma, NOS With Epstein-Barr Virus Positivity in an Elderly Patient With Myelodysplastic Syndrome: An Autopsy Case Report
Authors: Lanceta J , Xue W , Hurford M , Wu H 
Published: October 2020

Abstract

Casestudy
Epstein-Barr virus (EBV)-associated peripheral T-cell lymphomas are a group of aggressive neoplasms with a geographic predilection for South America and Asia, but are very rare in Western populations.

Results
We report a case of a 74-year-old Caucasian female who presented with pancytopenia and B symptoms with EBV-IgG detected on admission. Past medical history included: ITP, chronic urticaria, and recently diagnosed myelodysplastic syndrome (MDS) on bone marrow biopsy one month prior to admission. Excisional biopsies of an enlarged right neck lymph node (repeated within 6 months) and right axillary lymph node five years ago were negative for a lymphoproliferative disorder at the time. Repeated bone marrow biopsy, performed during the current admission, confirmed the diagnosis of MDS, with scattered T-cells without aberrant immunophenotype. Despite aggressive treatment from multiple specialties, the patient deteriorated and expired four weeks later from complications of MDS. At autopsy, there was diffuse lymphadenopathy involving the mediastinum, axilla, pelvis and peripancreatic fat. Lymph node sections demonstrated nodal architecture effacement by diffuse, vaguely nodular lymphoid infiltrates.
Histologically, the infiltrates were composed of medium to large lymphocytes with round to slight irregular nuclei, rare Reed-Sternberg-like multinucleated cells, clumped chromatin, and indistinct nucleoli. Individual cell necrosis was abundant with mitotic figures readily identifiable. Immunohistochemistry revealed CD2+ CD3+ neoplastic T-cells that co-express MUM1 and a subset of CD30, while negative for CD4, CD5, CD8, CD56, ALK1, and TDT. EBV-encoded RNA in-situ hybridization was focally positive. The final postmortem diagnosis was peripheral T-cell lymphoma, not otherwise specified (NOS), with focal EBV positivity.

Conclusion
Co-existence of a de-novo MDS and non-Hodgkin lymphoma without any prior chemotherapeutic exposure is a highly unusual finding, although MDS-like presentations can occur with EBV-associated lymphomas. Peripheral T-cell lymphoma, NOS is an aggressive lymphoma and EBV positivity has been found correlated with a poor prognosis. This case demonstrates how postmortem examination remains an important tool in clinical- pathological correlation and highlights the potential pathogenetic role EBV plays in MDS and T-cell lymphoma.
Brush Licking Toxicity: Toxin & Microorganism Growth On Paint Brushes
Authors: Hoang C , Flaws M , Moore N , Lerret N 
Published: October 2020

Abstract

Introduction/Objective
A common practice utilized by painters is licking their paint brush bristles to form a sharp point for fine lines and details. Literature details artists careless around their mediums have a higher incidence of becoming ill, yet if their brushes harbor any toxic substances or pathogenic bacteria it is currently unknown. Therefore, this study aims to determine if there is risk associated with brush licking, by determining if pathogenic bacteria and/or heavy metals are present on the brushes of volunteer artists.

Methods
We obtained 17 volunteer paint brushes and inoculated specialized collection and transport media (E- Swab, BD Biosciences, San Jose, CA) while the volunteer completed a qualitative de-identified survey indicating brush licking status. Brushes were swirled in the E-swab collection tube, then subbed to sheep blood agar plates and chocolate agar plates for bacteria growth analysis. Matrix-assisted laser desorption/ionization time-of-flight (MALDI- TOF) technology was used for identification. With the remaining E-Swab media, lead (3M, St. Paul, MN) and arsenic (HACH, Loveland, CO) testing using commercial kits was done. MALDI-TOF identification and heavy metal testing results were then compared to survey results.

Results
One of 17 specimens (6%) had pathogenic bacteria identified (Pseudomonas aeruginosa). This specimen’s survey also indicated routine brush licking. The sensitivity and specificity of MALDI-TOF for Pseudomonas aeruginosa is 96.67% and 97.87%, respectively. The remaining 16/17 (94%) had normal flora present. Importantly, the specimen containing Pseudomonas aeruginosa also had high levels of arsenic at 50 ppb. None of the specimen tested contained lead.

Conclusion
Our results indicated there is indeed some risk associated with brush licking. However, due to the small sample size, statistical significance could not be determined. Nonetheless, with the lack of knowledge surrounding this subject, it is beneficial to further explore and educate painters on the toxicities of brush licking.
Afirma Testing in Thyroid Nodules with Indeterminate Cytology: A single Medical Institute Experience
Authors: Yang Z , Zhang T , Layfield L , Esebua M 
Published: October 2020

Abstract

Introduction/Objective
About 10 to 30% of thyroid fine needle aspiration (FNA) nodules have indeterminate cytology, including Bethesda III, IV, and V. Afirma Gene Expression Classifier (GEC) measuring the expression of 167 mRNA was designed to classify the indeterminate thyroid nodules into benign and suspicious categories. This study aimed to evaluate the clinical performance of the Afirma GEC testing in these indeterminate thyroid lesions.

Methods
Medical records of patients with indeterminate thyroid FNA results and corresponding Afirma GEC results from November 2012 to December 2019 were retrieved. Subsequent surgical follow-up results were obtained. GEC results were compared to the histologic diagnoses.

Results
1. There were 77 cases with indeterminate thyroid FNA results. Cytology diagnosis included 67 Bethesda III and 10 Bethesda IV. Afirma GEC results were benign for 41 cases (53%), suspicious for 32 cases (42%), and non- diagnostic for 4 cases (5%). Twenty seven of 32 cases (84%) with suspicious GEC results had surgical follow-up which revealed 12 malignant and 15 benign histologic diagnoses. Only 11 of 41 cases (27%) with benign GEC results had surgery which showed 8 benign and 3 malignant diagnoses. Based on the data, the sensitivity of this test is 80% and specificity is 65%. Positive predictive value (PPV) is 44% and negative predictive value (NPV) is 73%.
The false positive cases include 5 Hurthle cell adenoma, 4 nodular hyperplasia, 3 follicular adenoma, 2 Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFPT), and 1 lymphocytic thyroiditis. The false negative cases include 2 minimally invasive follicular carcinoma (from same patient) and 1 papillary thyroid carcinoma.

Conclusion
1. We demonstrated in this study that a little more than half of the cases with indeterminate thyroid cytology had negative Afirma GEC results.
2.Afirma test has relatively low specificity (65%) and PPV (44%). The sensitivity (80%) and NPV (73%) is relatively higher but is lower than the values in most literature. This could be due to the fact that majority of the Afirma GEC negative cases in this study did not have surgical follow-up and the sample size is small.
3.Afirma GEC test is a relatively good “rule-out” molecular test for indeterminate thyroid nodules but is not a reliable “rule-in” test due to the low specificity and PPV.
Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL) Presenting As An Obstructive Pancreaticoduodenal Mass: A Case Report
Authors: Ritter J P , Flores R , Nazarullah A 
Published: October 2020

Abstract
Casestudy: A 74-year-old woman of Scottish descent presented with obstructive jaundice and weight loss. Imaging revealed a head of pancreas mass with extrahepatic bile duct dilation. Fine needle aspiration cytology of the mass was non-diagnostic, therefore the patient underwent a pancreaticoduodenectomy. Gross examination revealed a circumferential, necrotic lesion involving the periampullary duodenum with invasion into the pancreas and peri-pancreatic soft tissue. Microscopically, the lesion was composed of diffuse sheets of monomorphic medium-sized cells with fine chromatin, inconspicuous nucleoli, and scant pale cytoplasm. The duodenal mucosa overlying the lesion was ulcerated. Epitheliotropism was noted in the duodenal villi, crypt epithelium and pancreatic duct epithelium. The tumor showed extensive areas of necrosis and conspicuous perineural invasion. The duodenal mucosa uninvolved by the tumor showed no evidence of an underlying enteropathy, such as Celiac disease. By immunohistochemistry, the neoplastic cells were positive for CD45, CD3, CD8, CD56, TIA-1, granzyme B, TCR-BF1, and TCR-gamma, and were negative pan B-cell markers, CD4, CD5, CD25, CD30, EBER, HHV-8, and TCL-1. Molecular studies for T cell clonality revealed clonal TCR-alpha-beta and gamma-delta gene rearrangements. Given the morphologic and immunophenotypic findings, the diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) was rendered. This case is unique with features not typical of MEITL, namely mass-like pancreaticoduodenal presentation resulting in a Whipple resection, extensive necrosis, and perineural invasion.
Indeterminate Dendritic Cell Tumor (IDCT) of GI Tract, Lymph Node and Spleen Masquerading as Refractory Inflammatory Bowel Disease
Authors: Huang W , Bayerl M G 
Published: October 2020

Abstract

Introduction/Objective
Indeterminate dendritic cell tumor (IDCT) is an extremely rare neoplasm, most frequently presenting in skin with cells resembling precursors to Langerhans cells. We report an exceptional case of IDCT occurring in GI tract, spleen, and lymph nodes of a 66-year-old lady, mimicking inflammatory bowel disease (IBD).

Methods
Four years prior to the diagnosis of IDCT, she was diagnosed with ulcerative colitis (UC) based on bloody diarrhea and pan-colitis. Her colitis became refractory to medical treatments and she developed pancytopenia, splenomegaly and abdominal lymphadenopathy. A FNA of abdominal lymph node and a colonoscopic biopsy both showed non-necrotizing granulomas, which along with her multiple oral ulcers suggested Crohn’s disease. Due to failure to medical treatments, she underwent proctocolectomy and ileostomy, followed later by subtotal colectomy with excision of a splenule and lymph nodes.

Results
All specimens from the final operation showed involvement by IDCT characterized by polygonal cells with abundant eosinophilic cytoplasm, oval nuclei with occasional nuclear grooves, open chromatin and eosinophilic nucleoli. By immunohistochemistry, the tumor cells expressed S100, CD1a, cyclin D1, BRAFV600E. Langerin staining was observed in &lt;5% of cells, suggesting partial differentiation of tumor cells (frequently seen in IDCT) vs. reactive Langerhans cells. No overt cytological atypia and no necrosis were observed. Eosinophils, neutrophils, lymphocytes and plasma cells were sparse. There was no emperioloperesis. The colon showed multifocal active and chronic inflammation and ulcerations associated with the IDCT infiltrate. These specimens were diagnostic of IDCT.

Conclusion
Absence Langerin in the majority of cells excluded the possibility of Langerhans cell histiocytosis. The presence of CD1a and absence of bone involvement excluded the possibility of Erdheim-Chester disease.
Retrospectively, it appears that the patient’s symptoms were due to IDCT rather than IBD. The clinical course of IDCT is highly variable, but the BRAF mutation offers a promising new therapeutic target for this patient.
An Interesting Case Report of A Concurrent Classic Hodgkin Lymphoma and Gray Zone Lymphoma in the Mediastinum
Authors: Mai B , Huddin J , Hu Z 
Published: October 2020

Abstract

Casestudy
A 52-year-old female presented with night sweats, chills, anorexia, and weight loss. Computed tomography and positron emission tomography showed a soft tissue infiltration in the anterior mediastinum and hypermetabolic bilateral supraclavicular, mediastinal, right hilar, and left internal mammary lymph nodes. An anterior mediastinal mass resection and thymectomy was subsequently performed.

Results
Sections of the mediastinal mass showed Hodgkin/Reed-Sternberg cells (HRS) admixed with small lymphocytes, histiocytes, plasma cells, and eosinophils. The HRS cells are positive for CD30, CD15, and MUM1, faintly positive for PAX5, and negative for CD20, CD45, CD79a, and BCL6. The morphology and immunophenotype is diagnostic of nodular sclerosis classic Hodgkin lymphoma (CHL). Sections of the thymectomy specimen showed similar morphology, however, in an area that represents 10-20% of the specimen, there are nodular and diffuse lymphoid infiltrates consisting of small lymphocytes, histiocytes, and large atypical cells. The large atypical cells are positive for CD20, CD23, CD30, CD45, CD79a, BCL2, BCL6, MUM-1, and PAX5, and negative for CD1a, CD3, CD57, and Cyclin D1. The background small CD3-positive lymphocytes form a rosette around most of the large atypical cells. CD21 and CD23 stains highlight residual follicular structures. In situ hybridization for EBV-encoded RNA (EBER) is negative. The presence of residual follicular meshwork with an immunophenotype of large B cell lymphoma supports a diagnosis of a gray zone lymphoma (GZL). Overall, CHL is involving 80-90% and GZL is involving 10-20% of the thymic tissue. The patient was subsequently placed on ABVD chemotherapy and achieved remission.

Conclusion
An accurate diagnosis of GZL is challenging. GZL is a rare type of lymphoma with morphological features between CHL and diffuse large B-cell lymphoma (DLBCL). It is even rarer to encounter a CHL concurrently present with a GZL. The optimal therapeutic approach for cases with concurrent lymphoma diagnosed with CHL and GZL needs further investigation.
Leveraging Existing Institutional Resources to Maintain Quality Assurance Practices in Anatomic Pathology in the Era of Social Distancing
Authors: Arriola A , Aneja A , Rong Y , Taraif S , jhala N 
Published: October 2020

Abstract

Introduction/Objective
Due to the COVID-19 pandemic, hospitals had to adapt practices to incorporate social distancing while maintaining quality assurance (QA) in anatomic pathology (AP). Prior to this, our general surgical pathology (SP) and cytopathology (CP) services held daily consensus conferences (CC) at a multi-headed microscope. Implementing social distancing meant only a few faculty were present onsite and avoidance of interactions at the multi-headed scope. In an effort to preserve QA through CC, faculty exploited the use of web conferencing through our HIPAA-compliant Zoom. We describe the utility of this new practice.

Methods
From 3/25-4/30/20, all SP and CP cases selected for CC were presented by respective pathologists (n=8) in their own offices by using individual microscopes with cameras, image acquisition software, and screen-sharing through Zoom. One pathologist was responsible for sending out a new CC Zoom link daily and recording the consensus diagnosis. All onsite pathologists and those at home participated.

Results
We presented 95 SP and 31 CP cases through Zoom compared to 300 SP and 60 CP cases presented at a similar timeframe prior to social distancing. This 68% and 48% decline could be attributed to elective procedure cancellation. We assigned a consensus diagnosis to all cases, with 77% overall being malignant diagnoses, and breast being the most common SP specimen type (22%). Additionally, all participating pathologists felt comfortable with the new format irrespective of being onsite or at home. Apart from minor audio issues, we did not notice significant lag time or visual disturbances that interfered with diagnostic abilities. Importantly, the transition did not involve investing in new technology.

Conclusion
The new virtual CC allowed our department to maintain QA practices in AP without sacrificing quality and serves as a starting point to investigating the use of this technology to other applications in AP, such as overnight frozen sections.
Optimizing the Handling of Invasive Fungal Sinusitis Surgical Specimens
Authors: Ababneh E , Dermawan J , Thomas M , Wang X , Blank A , Bakhshwin A , Terzioglu M , Miller B , Shah A , Griffith C , Chute D 
Published: October 2020

Abstract

Introduction/Objective
Invasive fungal sinusitis (IFS) is an aggressive disease characterized by invasion of fungal hyphae into tissue/neurovascular bundles. This project assessed the handling of IFS specimens and implemented protocols to improve turnaround time (TAT).

Methods
A retrospective review of cases accessioned with a clinical concern for IFS from 2014-2019 was performed. TAT for each step in the specimen processing was recorded. A flowchart was created using stakeholder interviews and a revised protocol was developed after assessing critical needs. Assessment of interventions was performed following implementation of the new protocol. The protocol will be evaluated by prospective direct case-by-case feedback and after a 6-month interval (projected August/2020). At 6-months, goals are a 24 hours median time between frozen section and sign-out and elimination of outliers (greater than 2 working days).

Results
We identified 53 specimens from 32 patients in the pre-intervention period (36 cases positive for IFS). Median time from frozen section to final sign-out was 28 (5-312) hours. Four areas for improvements were identified:
(1) triaging specimens to different protocols according to arrival time, (2) optimized triaging for available histology processors, (3) standardized GMS ordering, and (4) standardized case delivery/communication with sign-out staff. Interventions include: protocol for processing specimens based on time of day, new histology protocols to expedite GMS performance, an email group for rapid communication with staff pathologists and histology, and a worksheet/checklist to track each case. After implementation of the protocol, 8 cases from 7 patients were received. Median time from frozen section to final sign-out was reduced to 20 (2 – 50) hours.

Conclusion
The protocol for handling IFS specimens became live on 2/1/2020. It has reduced TAT of suspected IFS cases, from a median of 28 hours to 20 hours. The longest interval to sign-out went from312 hours to 50 hours.