bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Study of SARS-CoV-2 Antibody Characteristics Using Label-Free Immunoassays
Authors: Luo Y R , Yun C , Wu A H , Lynch K L , Chakraborty I 
Published: October 2021

Abstract

Introduction/Objective
Since the start of the COVID-19 pandemic, much research has focused on the kinetics and magnitude of humoral immune response. With the advantages of monitoring real-time immunoreactions, label-free immunoassay (LFIA) is becoming a powerful tool in serology studies. We have developed LFIAs to measure SARS- CoV-2 antibody avidity and neutralization activity in a cohort of COVID-19 patients and determine if they correlate with antibody concentration. Serial serum samples collected from mild to severe COVID-19 patients were measured out to 8 months post-symptom onset to determine the durability of the neutralizing antibody response.

Methods/Case Report
Based on thin-film interferometry technology, we established a label-free IgG avidity assay and a label-free surrogate virus neutralization test (LF-sVNT). For measurement, sensing probes pre-coated with receptor-binding domain (RBD) of SARS-CoV-2 spike protein are applied to serum samples containing SARS-CoV-2 antibodies. The label-free IgG avidity assay measures the binding strength between RBD and IgG under urea dissociation. The LF-sVNT analyzes the binding ability of RBD to ACE2 after neutralizing RBD with antibodies.

Results (if a Case Study enter NA)
IgG avidity indices and neutralizing antibody titers (IC50) were determined from serum samples (n=246) from COVID-19 patients (n=113). IgG concentrations were measured using a fluorescent immunoassay. The neutralizing antibody titers showed a weak correlation with IgG concentrations and no correlation with IgG avidity indices. Over the time course up to 8 months post-symptom onset, IgG concentrations and neutralizing antibody titers presented similar trends: an initial rise, plateau and then in some cases a gradual decline after 40 days. The IgG avidity indices, in the same cases, plateaued after the initial rise.

Conclusion
The results demonstrated that LFIA could be used an excellent solution in the determination of SARS- CoV-2 antibody characteristics. The study found that IgG concentration and neutralizing antibody titer declined over time, while IgG avidity index remained constant after reaching a plateau. The decline of antibody neutralization activity can be attributed to the reduction in antibody quantity rather than the deterioration of antibody quality, as measured by antibody avidity.
Excellence in Laboratory Practice with the Validation of Opiate Confirmation using Liquid Chromatography/Mass Spectrometry
Authors: Dalal S , Jhala D 
Published: October 2021

Abstract

Introduction/Objective
Veterans are more susceptible to opioid addiction as they are more likely to suffer from chronic pain which leads to increased need of confirmed identification of opiates in toxicology laboratories. Gas chromatography-mass spectrometry (GC-MS) had been a long-accepted method for the quantitative analysis of opiates in urine, but requires tedious, time-consuming, and complex sample preparation steps. On the other hand, liquid chromatography-mass spectrometry (LC/MS) has comparatively simpler sample preparation steps, can handle three times the number of specimens, much faster turnaround times and produces equally valid results. However, the validation experience of this simpler detection method has not been well published, particularly in a Veterans Healthcare Clinical Laboratory setting.

Methods/Case Report
The quality assurance goal of the validation is to demonstrate that the Agilent 6410 Triple Quadrupole LC/MS (Wilmington DE) is able to identify the same opiate drug analytes performed by the GC-MS. Method to method correlation, within run precision, day to day precision, carryover study, matrix (ion) suppression study, and a limit of detection study were performed as part of this validation.

Results (if a Case Study enter NA)
For the total of 156 specimens run for the method comparison, there was 94.9% agreement, or 148/156 samples were concordant. The 8 discrepancies had drugs that were present below the cutoff limit of the LC/MS. Within run precision with 20 replicates of negative, positive, and at the cutoff were run with all results as expected. The day to day precision of a positive and negative sample run over 10 days also yielded results as expected. The carryover study demonstrated minimal carryover. The matrix (ion) suppression study showed ion suppression at 16.8%, which is below the amount needed to affect analyte concentrations. The LC/MS was highly sensitive with a limit of detection of &gt;97% at 25 ng/mL. Thus, the result of comparison showed good concordance.

Conclusion
LC/MS is a simpler, more efficient method of opiate testing that is comparable to GC-MS for the detection of opiate drugs of abuse in urine. This is an example of excellence in laboratory practice by extending the best quality laboratory care with proper validation of instrument methods conducive to laboratory workflow.
A Unique Case of der(16)t(1;16) Identified in B-Lymphoblastic Leukemia
Authors: Fenu E M , Lyalin D , Insuasti-Belrtran G , Beaty M , Pettenati M , Maracaja D 
Published: October 2021

Abstract

Introduction/Objective
A derivative chromosome 16 is rare in hematologic malignancies. There are only two previously reported cases to date, both associated with acute myeloid leukemia (AML). In these cases, the t(1;16) presented as a der(16)t(1;16) resulting in trisomy 1q. This was the sole anomaly in each case. Cytogenetic abnormalities in B-ALL are common and important for understanding of the pathogenesis, classification and prognosis of the disease. Herein we describe a case of der(16)t(1;16)(q12;q24) identified for the first time in a patient with B-cell acute lymphoblastic leukemia (B-ALL), with correlation with morphologic and immunophenotypic findings.

Methods/Case Report
The patient is a 65 year-old male who initially presented with one week of fatigue. A complete blood count showed leukocytosis (white blood cell count of 24.6 x 103/uL), anemia (hemoglobin of 7.9 g/dL), marked thrombocytopenia (platelets of 5 x 103/uL). A differential showed 64% blasts and peripheral blood flow cytometry confirmed B-lymphoblastic differentiation, with two distinct immunophenotypic populations. The patient’s bone marrow biopsy was hypercellular (&gt;95% cellularity) with panhypoplasia and a marked increase in blasts (88% by aspirate manual differential). Cytogenetic analysis of the bone marrow also demonstrated the presence of two clonal cell lines. The first cell line was chromosomally normal, while the second had a t(9;22) translocation and a derived chromosomes 16 from a t(1;16). FISH analysis confirmed 59% of cells demonstrated a BCR/ABL1 fusion event.

Results (if a Case Study enter NA)
NA

Conclusion
The patient’s der(16)t(1;16)(q12;q24) represents a novel genetic abnormality that has not previously been reported in B-ALL. Although it has been described in other acute leukemias, little is known about this abnormality in B-ALL and its implications in pathogenesis and prognosis. Additional molecular testing, including chromosomal microarray analysis, mate-pair, or long-range DNA sequencing or RNA sequencing, could potentially identify the fusion partners and shed light on pathophysiological mechanisms implicated in the leukemic process.
Merkel Cell Carcinoma Presenting as a Malignant Pleural Effusion Post-COVID-19 Hospitalization: a Case Report and Literature Review
Authors: Toprak M , Lanceta J , Rosca O C 
Published: October 2021

Abstract

Introduction/Objective
Merkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine carcinoma of the skin, associated with immunosuppression, UV light exposure, and the Merkel cell polyomavirus (MCPyV). Metastatic MCC diagnosed in body fluid cytology is extremely rare. Here, we report on a case of a 65-year-old male presenting with a right pleural effusion and a remote history of MCC, unknown to us during the cytologic evaluation of the effusion. To the best of our knowledge, this is the sixth case of metastatic MCC diagnosed in body fluid cytology reported in English literature, and the first one reported in a patient previously admitted for COVID-19 pneumonia.

Methods/Case Report
A 65-year-old male presented with dyspnea and acute hypoxic respiratory failure. Past medical history was significant for squamous cell carcinoma of the right forearm excised four months prior and ulcerative colitis. The patient had two recent hospitalizations for COVID-19 pneumonia. Chest x-ray on admission demonstrated an enlarged, loculated right pleural effusion. Emergent thoracentesis was performed and 1500 cc of bloody pleural fluid was sent for cytology. The patient’s respiratory status improved. A ThinPrep and a cell block were prepared. Both displayed clusters of small round blue cells with hyperchromatic nuclei, scant cytoplasm, and fine chromatin in a background of rare mesothelial cells, macrophages, and numerous lymphocytes. Immunohistochemical (IHC) studies showed CK20, AE1/AE3, and CAM 5.2 in a perinuclear dot-like staining pattern. CD56, chromogranin, and synaptophysin were also positive. Ki-67 proliferative index was about 40%. TTF-1 was negative, while CD45 highlighted background lymphocytes. The primary care physician was contacted and the patient’s past medical history was significant for MCC. Subsequent MCPyV and SATB2 demonstrated nuclear positivity in the tumor cells. Diagnosis of MCC was done.

Results (if a Case Study enter NA)
NA

Conclusion
MCC is a highly aggressive malignancy rarely reported in body fluids. MCC should be included in the differential diagnosis of malignant pleural effusions, especially in cases of the small blue round cells. Using IHC, like CK20 and neuroendocrine markers including the newer SATB2, can lead to an accurate diagnosis. Additional reporting of such cases may increase awareness, especially where prior history is not readily available, such as in this present instance.
Accuracy of the Milan System for Detecting Neoplastic vs Non-Neoplastic Salivary Gland Lesions: A Retrospective Review
Authors: Fakhri N , Khokhar H , Khreefa Z , Shahmirzadi M , Bhalla R 
Published: October 2021

Abstract

Introduction/Objective
Overlapping morphology and heterogeneity of salivary gland tumors (SGT) poses a diagnostic challenge. FNA is commonly used diagnostic tool for evaluation of superficial and deep lesions of any site, but above limitations restrict its maximum utility. To standardize reporting and to address above limitations, Milan system (MS) of reporting salivary gland cytology, has been developed and implemented by labs. We conducted a retrospective study, applying MS to salivary gland lesions (SGL) to evaluate its accuracy and usefulness in discriminating between neoplastic and non-neoplastic conditions, and thus directing patient management (PM)

Methods/Case Report
10 yr retrospective review was performed to include patients with FNA for SGL, cytology diagnosis categorized using MS, cytology-histology (CH) correlation performed, and patients’ charts reviewed for follow up. Attention given to diagnostic discrepancies between MS categories and the histologic diagnosis

Results (if a Case Study enter NA)
152 patients (20-88yrs) were retrieved, peak incidence 40-49 yrs; M:F ratio 1.2:1. Distribution of the cases in the MS categories: Non-diagnostic (ND) 24, Non-neoplastic (NN) 33, Atypia of Undetermined Significance (AUS) 4, Neoplasm (N) 71, Suspicious for malignancy (SUN) 7, and Malignant (M) 10. 60 cases identified with follow-up histology, of which 51 cases were correlated, distributed as 4 ND, 4 NN, 0 AUS, 37 N, 3 SUN, and 3 M. The uncorrelated 9 cases were distributed as 4 ND due to scant sampling; 2 NN, histologically Warthin’s tumor and sialolipoma; 2 AUS, histologically basal cell neoplasm and infarcted Warthin’s tumor; 1 malignant, histologically cystic mucoepidermoid carcinoma; 0 cases for neoplastic and suspicious for malignancy categories

Conclusion
Milan System is a useful cytologic tool for diagnosing and segregating patients with salivary gland pathologies, however, our study shows MS to be more reliable diagnostic tool with higher accuracy (combined 98%) in N, SUN & M categories as compared to ND, NN & AUS categories (combined 50%)
Diffuse Idiopathic Neuroendocrine Cell Hyperplasia (DIPNECH) on Electromagnetic Navigation Bronchoscopy (EMN) Guided Fine Needle Aspiration (FNA): A Case Report
Authors: Alfattal R , Palacio D M , Shah S , Nawgiri R , Muthukumarana P V 
Published: October 2021

Abstract

Introduction/Objective
DIPNECH is a clinicopathological diagnosis characterized by abnormal proliferation of single or clusters of neuroendocrine cells in the bronchial mucosa. The World health organization includes DIPNECH as a preinvasive lesion to carcinoid tumors of the lung. Diagnosis is often delayed or missed due to insidious presentation and rarity of the disease. High degree of suspicion in the appropriate clinical and radiological context is important for early diagnosis. We describe a unique case of DIPNECH diagnosed by EMN guided aspiration cytology in the setting of multiple incidental lung nodules and confirmed on surgical resection.

Methods/Case Report
A 69-year-old female with history of insidious cough was referred to pulmonology clinic for multiple incidental bilateral lung nodules detected by CT scan, largest involving the right middle lobe. Although the main diagnostic consideration was pulmonary metastasis, several radiological features, including diffuse mosaic attenuation pattern, prompted the possibility of a diffuse neuroendocrine process. Electromagnetic navigation bronchoscopy (ENB) guided fine needle aspiration cytology was performed. Air-dried and Papanicolaou stained smears were scant but showed dispersed and clusters of small cells with fine chromatin with minimal cytoplasm. No necrosis or mitosis were seen. A cell block was prepared that showed rare clusters of tumor cells positive for immunostains synaptophysin, chromogranin, CD56, with a Ki-67 of 1%. In the appropriate clinical and radiological context findings were consistent with a well differentiated neuroendocrine process such as DIPNECH. Right middle lobe resection confirmed extensive DIPNECH with multiple typical carcinoid tumors and tumorlets.

Results (if a Case Study enter NA)
NA

Conclusion
It is essential to be familiar with the clinical and radiological findings of DIPNECH and include it in the differential diagnosis of its mimickers. Although the diagnosis is challenging on limited specimens, this report indicates that EMN guided aspiration cytology can be used as a valuable early tool for accurate diagnosis and timely management of DIPNECH.
Reactive Cellular Changes in Anal Cytology Smears and Its Relation to Future Dysplastic Changes in HIV+ Subjects
Authors: Seydafkan S , Loukeris K , Pincus M R 
Published: October 2021

Abstract

Introduction/Objective
The incidence of anal squamous cell carcinoma is increasing in high risk populations. There is no consensus regarding screening for anal squamous cell carcinoma. Anal pap smears are interpreted using the Bethesda System for cervical cytology. Significant challenges exist for anal cytology that do not apply to cervicovaginal cytology.

Methods/Case Report
We retrospectively reviewed the anal cytology smears performed in our institution between 2012- 2019. The smears with reactive cytology changes (RCCs) were retrieved, and corresponding follow up smears were reviewed.

Results (if a Case Study enter NA)
A total of 39 cytology smears with positive RCCs with no dysplasia diagnosis were obtained. All were HIV+. 32 cases were male and 7 females. The overall mean age was: 37.77 + 11.94 SD (range: 23-65 years). The mean age for men was 36.53 + 11.51 and 43.43 + 13.13 for women. Although this mean age was higher for women, the age difference was statistically insignificant (p=0.7, alpha=0.05). Four of the women patients had concomitant cervicovaginal cytology all of which were negative. Only 1 female had a follow up study which was negative. Of the 39 cases, 26 cases (25 men and 1 woman or a total of 66.7%) had followed up smears versus 13 (33.3%) cases with no follow up. A total of 7 out of the 26 follow ups were negative for dysplasia (26.92%). Of the 26 follow ups, a total of 18 (69.23%) were found to have progressed to either ASCUS (15 or 57.69%) or LSIL (3 or 11.53%). One ASCUS was diagnosed as possible high grade. The mean time to convert to dysplasia was 2.06 + 1.25 years (range 1-5 years). Half of the dysplastic cases developed in a 1 year period.

Conclusion
Patients who have reactive changes on anal cytology should be monitored for possible development of anal neoplasia.
Meningothelial Hamartoma of the Scalp: Clinicopathologic Review of an Unusual Tumor Mimicking a Vascular Neoplasm with Review of Literature
Authors: Li L , Suster D 
Published: October 2021

Abstract

Introduction/Objective
Benign meningothelial hamartoma of the scalp is a rare entity with only scattered case reports existing in the literature. The hamartomatous process is believed to occur secondary to ectopic displacement during embryogenesis with the migration of meningothelial cell precursors to the incorrect location or secondary to an obliterated meningocele. This tumor may be easily missed and may be misdiagnosed as lipoma or sometimes as cutaneous angiosarcoma due to the several histologic features that mimic the histology of a vascular neoplasm.

Methods/Case Report
We report an unusual benign skin lesion occurring in a 19-year-old man with no significant past medical history. The lesion had been present since he was an infant and had been slowly enlarging over the past 15 years. The lesion caused pain and discomfort and the patient underwent an excisional biopsy of the lesion. Histologic examination showed a subcutaneous lesion with ill-defined borders and peripheral areas of infiltration between adnexal structures. Immunohistochemistry performed on the tumor cells showed that they were positive for EMA, progesterone receptor, D2-40, and vimentin. A next-generation sequencing study using a hybrid capture-based panel examining 50 commonly mutated genes in human neoplasia was performed and showed no molecular alterations supporting the benign or non-neoplastic nature of the lesion. Along with this case, we review 20 cases of meningothelial hamartomas from 13 papers and summarize them in the table.

Results (if a Case Study enter NA)
N/A

Conclusion
To our knowledge, this is the first reported case of one of these lesions with associated molecular genetic testing. The molecular study carried out, in this case, did not disclose any genetic variants commonly associated with human neoplasia supporting the notion that this lesion does not represent the neoplastic process but rather a hamartomatous process. Meningothelial hamartoma is an exceedingly rare, benign lesion that may be confused with a low-grade vascular neoplasm due to its rare nature and unusual histologic features.
Solid Cell Nests Hyperplasia (Ultimobranchial Body Remnants) of the Thyroid: A Pitfall
Authors: Bharadwaj H , Khan A 
Published: October 2021

Abstract

Introduction/Objective
Solid cell nests (SCN) are small epithelial cell nests interspersed within thyroid parenchyma, resembling squamous/transitional epithelium. SCNs, which are ultimobranchial remnants, are popularly considered pluripotent stem-cells responsible for developing follicular and C-cells. While SCNs are not an uncommon incidental findings in thyroid, solid cell nest hyperplasia is rare. SCNs are often mistaken for benign entities such as C-cell hyperplasia (CCH) or malignant lesions such as papillary thyroid carcinoma (PTC), metastatic squamous cell carcinoma, or medullary thyroid microcarcinoma (MTC).

Methods/Case Report
To reiterate this diagnostic dilemma, we present a case of a 57-year-old male with a six-year history of Hashimoto thyroiditis and multiple bilateral thyroid nodules. Ultrasonography revealed two nodules, one in each lobe, measuring 2.0x1.9x1.8cm(right) and 1.6x1.5x1.5cm(left). Both were solid, hypoechoic nodules with smooth margins and no echogenic foci. Fine-needle aspiration of right nodule was suspicious for follicular neoplasm, Hürthle- cell type, and the left nodule was atypia of unknown significance. Right-hemithyroidectomy specimen revealed follicular adenoma and oncocytic adenomatous nodules in a background of florid lymphocytic thyroiditis (Hashimoto). In two blocks, small solid nests of cells were identified, largest focus measuring 0.5 cm. The cells were polygonal to epithelioid with moderate amphophilic cytoplasm. Nuclei were centrally located, irregular to oval with occasional grooves. While nests had a squamoid appearance, they did not have intercellular bridges. Although nuclear grooves and evenly dispersed chromatin and chromocenters were noted, they lacked optical clearing or intra-nuclear inclusions characteristic for PTC. Thus, excluding these two possibilities, primary diagnostic considerations were SCN versus CCH. Immunohistochemical analysis showed cells positive for P63 and CK5/6 and negative for PAX-8, TTF-1, thyroglobulin, CEA, and calcitonin.

Results (if a Case Study enter NA)
NA

Conclusion
If wrongly diagnosed as CCH, patients may be placed in a high-risk category for possible development of MTC. It is, thus, necessary to be aware of SCN, which can occasionally become hyperplastic, to prevent misdiagnosis.
The Variations of Insulin-like Growth Factor 1 Measured between Siemens Immulite, DiaSorin Liaison and IDS iSYS
Authors: Lee J K , Li S 
Published: October 2021

Abstract

Introduction/Objective
Insulin-like Growth Factor 1 (IGF-1) is a biomarker for the evaluation of growth hormone activity in the hypothalamic-pituitary axis. The current most common methodology for IGF-1 measurement is automated immunometric assays. In this study, we compared the IGF-1 on Siemens Immulite 2000, DiaSorin Liaison XL and IDS iSYS.

Methods/Case Report
Residual 30-110 serum specimens were randomly selected from routine hospital orders. IGF- 1 was measured on these three platforms and compared with Passing-Bablok regression. Bias was evaluated using the Bland-Altman method.

Results (if a Case Study enter NA)
Weighted Deming regression analysis showed approximately 80% and 56% positive bias on IDS iSYS and DiaSorin Liaison, compared with Siemens Immulite (iSYS=1.81*Immulite-117.65, r=0.91; Liaison=1.56*Immulite-4.58, r=0.98). There was approximately 8% positive bias on Liaison, compared with iSYS (Liaison=1.08*iSYS+0.56, r=0.99). The Passing-Bablok regression analysis revealed approximately 67% and 54% positive bias (iSYS=1.67*Immulite-75, r=0.91; Liaison=1.54*Immulite-3.44, r=0.91). Approximately 8% positive bias on Liaison was observed, compared with iSYS (Liaison=1.08*iSYS+5.65, r=0.99). The Bland-Altman plot showed the agreement between iSYS and Immulite IGF-1 was on average 129.6±123.3 ng/mL, 98.6±148.8 ng/mL between Liaison and Immulite and 37.0±46.5 ng/mL between Liaison and iSYS.

Conclusion
Immunoassays rely on the specificity of antibodies. There are wide variations between different immunoassay platforms for IGF-1 measurement. The standardization of IGF-1 assay is lack. It would be a challenge for clinicians to monitor IGF-1 or treat the patients with pituitary disorders, when switching to another platform. The potential impact of the variations in IGF-1 measurement between different immunoassay platforms should be aware.