bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sporadic Uterine Cervical Angiomyolipoma with Concurrent Endometrial Adenocarcinoma
Authors: Masoud M A , Wei E 
Published: October 2021

Abstract

Introduction/Objective
Angiomyolipoma is a benign mesenchymal neoplasm composed of variable admixture of thick dysmorphic blood vessels, smooth muscle cells, and fat cells that commonly arises in the kidney. It is strongly associated with tuberous sclerosis but it can also occur as sporadic. Extra renal angiomyolipomas have been reported with the liver being the most common location. Few cases of angiomyolipoma in the female genital have been reported where the uterus being the most common site. Uterine cervical angiomyolipoma has rarely been reported.

Methods/Case Report
We reported a case of 64-year-old white female with postmenopausal bleeding. Endometrial biopsy revealed endometrioid type endometrial adenocarcinoma. MRI showed endometrium was thickened, and the cervix was enlarged with disruption of the cervical fibrous stroma on the anterior surface concerning for cervical stromal invasion. Grossly, besides the polypoid mass that involved the endometrial cavity, there was a firm nodule with whorled cut surface noted on the anterior surface of the cervix.
Microscopic examination of the cervical nodule revealed a classic variant of angiomyolipoma with mature adipocytes, spindle shaped smooth myocytes and anomalous thick-walled blood vessels with hyalinization. The spindle cells were positive for smooth muscle actin and caldesmon. CD34 highlighted the thick walled blood vessels. The stain for HMB- 45 was negative in contrast to renal counterpart. These findings are consistent with cervical angiomyolipoma. In addition, there was endometrioid endometrial adenocarcinoma, FIGO grade 1, with microsatellite stable phenotype, with only superficial invasion of myometrium, without involvement of cervical stroma.

Results (if a Case Study enter NA)
NA

Conclusion
This is a rare and probably the only presentation of cervical angiomyolipoma concurrently occurring with endometrial adenocarcinoma. It is uncertain if these two disease entities have genetic or pathogenesis association. The imaging studies were very concerning for cervical stromal invasion or questionable cervical cancer with local invasion. Cervical angiomyolipomas, though, extremely rare, may also be included in dysfunctional uterine bleeding differential diagnosis.
Endometrial Adenocarcinoma Biopsies: Can Targeted Education Increase Reproducibility and Is It a Good Idea?
Authors: Petty D , Blankenship H , Beuerlein W , Naal T , Li W 
Published: October 2021

Abstract

Introduction/Objective
Assessing p53 mutation on biopsies could provide prognostic and therapeutic planning information, as it predicts worse outcomes for patients with endometrioid adenocarcinoma (EA). Immunohistochemistry (IHC) mutation pattern staining varies, easily causing misinterpretation. This study was designed to see if education clarifying staining issues would increase reproducibility, and if mutations detected in this setting were of prognostic import.

Methods/Case Report
p53 IHC on 46 FIGO grade 1 EA biopsies was scored by blinded participants. Education was provided regarding internal controls (IC), and common misinterpretations. The participants rescored to assess reproducibility. Outcome parameters (clinical stage [CS], progression free survival, higher FIGO grade on resection, and presence of mismatch repair mutations) were also assessed.

Results (if a Case Study enter NA)
25% of scores changed post-education. Intraclass correlation among raters was 0.29 pre and 0.43 post (from fair to moderate). Mutation status changed in 5 cases. 2/5 caught IC failure for 1 case. Post-participation surveys found 0 participants were previously familiar with “high wild type,” and 60% were unfamiliar with cytoplasmic staining pattern, the possibility for heterogeneity, and necessary ICs. Every participant agreed grading was easier following education. Out of 6 patients with high CS disease (IIIC-IV), none had p53 mutation. 2/11 cases with higher FIGO grade (2-3) on resection had mutation. One patient had recurrence with no detectable mutation. 15/46 patients had MMR results available. No p53 mutation was detected in those with a loss of MLH1 and PMS2 (n=8).

Conclusion
Education on IHC issues can increase reproducibility in scoring, though overall reproducibility on biopsies was still subpar. Mutation detected in this setting did not correlate with current outcome parameters. Given the possibility of heterogenous expression and difficulties interpreting edge effect and assessing ICs in scant specimens, p53 IHC on EA biopsies is not recommended.
Sinonasal teratocarcinosarcoma, A rare neoplasm; Case report and literature review
Authors: Waleed M , Murtaza F , Khan M , Khurram M S 
Published: October 2021

Abstract

Introduction/Objective
Sinonasal teratocarcinosarcoma (SNTCS) is an unusual neoplasm with high malignant potential. Histologically it consists of epithelial and mesenchymal constituents, with a combination of teratoma and carcinosarcoma. It primarily occurs in the nasal cavity and paranasal sinuses. This aggressive neoplasm has a high recurrence rate with a five-year survival of 30-50 percent. To this date, less than a hundred cases have been mentioned in the literature. Early diagnosis and management of the tumor can enhance the prognosis.

Methods/Case Report
We present to you a case of a 63-year-old woman presenting with epistaxis, nasal congestion, and blockage. The tumor was completely removed surgically and postoperative radiation therapy was given. Grossly the tumor was gray-white, with a solid texture. Postsurgical microscopic examination of the sections from different areas showed variegated appearance having a mix of teratoid; carcinomatous; sarcomatous and primitive neuroectodermal elements. Immunohistochemical staining revealed tumor cells expressing desmin, EMA, and cytokeratin. The follow-up examination was done after a year and showed no sign of recurrence.

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

Conclusion
Because of the scarcity and mixed cell lines of this tumor pathological diagnosis of the neoplasm is hard. Since this neoplasm is highly malignant and locally aggressive proper identification and removal are necessary for improving morbidity as well as mortality.
An Unusual Hematologic Manifestation in a COVID-19 Patient Treated with COVID-19 Convalescent Plasma
Authors: Andrzejewski C , Chakraborty S R , Stoddart L , Johari V 
Published: October 2021

Abstract

Introduction/Objective
A subset of Chronic Lymphocytic Leukemia (CLL) patients with COVID-19 may manifest rapid elevations in lymphocyte counts and poor clinical outcomes. Here we report our observations regarding this unusual hematologic manifestation in a CLL patient after he experienced a COVID-19 convalescent plasma (CCP) transfusion reaction.

Methods/Case Report
56-year-old A Rh- male with stable, treatment-naive CLL (13q deletion positive) diagnosed three years prior was admitted for COVID-19 hypoxia. Before developing COVID-19, baseline white blood cell (WBC) count was stable (~ 64 K/ mm3). Due to worsening hypoxia he was treated with an ARh+ High Titer CCP unit, Remdesivir, tocilizumab, and dexamethasone. The Blood Bank was notified of a possible CCP reaction and performed its standard workup which was adjudicated to be a febrile TACO reaction. During this evaluation it was noted that the patient’s WBC count had initially decreased to 46 K/ mm3, but rose on HD 3, to 78.4 K/mm3 and by discharge on HD 10 had increased to 200 K/ mm3. Flow cytometry revealed a B cell CLL immunophenotype. Post discharge day (PDD) 6 he developed herpes zoster. On post-discharge day (PDD) 7 his WBC count was 124K/mm3. By PDD 77 his WBC count had returned to baseline (~50 K/mm3).

Results (if a Case Study enter NA)
NA

Conclusion
The pt’s initial drop in his WBC count followed by a gradual rise has been observed in patients with severe COVID-19 independent of CCP infusion. Lymphocytosis in a subset of CLL patients with COVID-19 has been reported (termed “COVID-19 Induced Lymphocytosis” (CIL)) and, in contrast to our patient with an improved outcome, has been associated with severe/fatal outcomes. Of note these other patients did not receive CCP. Mechanisms related to CIL are unknown. Such poor clinical outcomes heighten the need for further studies of CIL. The role of CCP in affecting this process, if any, also merits further clarification.
Utilisation of Deep Learning-Enabled Image Analysis for Detection and Enumeration of Plasmodial Forms in Red Cells
Authors: Hu K , Welch W , Pilichowska M , Bacsa D , Vandenhirtz J 
Published: October 2021

Abstract

Introduction/Objective
Objective: This work investigates utilisation of deep learning enabled peripheral blood smear image analysis for automated detection and enumeration of red cell parasites.

Methods/Case Report
Methods: Peripheral blood smear red cell images from 30 individuals identified as positive and/or negative for plasmodilum falciparum forms were used. Blood submitted to hematology laboratory for complete blood count was evaluated on Sysmex XN 3100 analyzer with routine peripheral blood slides performed on instrument associated SP50 stainer. Images of red cells obtained with Xfinity DX40 microscope mounted camera were subjected to classification using deep learning software (Cognex, ViDi Suite 4.1). The training of the classification tool was performed on 200 peripheral blood smear images divided in two dataset classes: normal/negative and abnormal/positive for plasmodia, 50% of training images represented positive data set. Performance of the developed model was tested on 300 images including 66% positive for plasmodia obtained from 20 patients. Enumeration of parasitic forms was performed for each case. Model performance was compared to expert hematopathology reviewer which was used as gold standard.

Results (if a Case Study enter NA)
Results: Overall, Cognex ViDi Suite 4.1 demonstrates the effectiveness in discriminating between images positive and negative for red cell plasmodial forms as well as enables parasite quantification. Following performance specifications were determined for parasite detection: sensitivity (0.969230769), specificity (0.99383217). High correlation coefficients (0.9961) between automatically detected parasites and ground truth, on both image level and patient level, demonstrate the practicality of our method.

Conclusion
Deep learning enabled image analysis of peripheral blood smears is a promising alternative to manual identification and enumeration of red cell plasmodial forms with performance comparable to expert hematopathology reviewer.
Valproic Acid Induced Thrombocytopenia and Dysmegakaryopoiesis in a Pediatric Patient
Authors: Langlie J , Huberman M , Akgun Y 
Published: October 2021

Abstract

Introduction/Objective
Valproic acid is a branched short chain fatty acid derivative that is used primarily to treat epilepsy as well as mood disorders, certain types of headaches, and neuropathic pain. It is commonly prescribed in the pediatric population and has shown to be effective for refractory epilepsy with adequate seizure control. Serious side effects may be prominent if the medication is not kept at the therapeutic range. A wide variety of known hematologic problems can be encountered including but not limited to anemia, thrombocytopenia, and leukopenia.

Methods/Case Report
We present a case of a pediatric patient with a past medical history significant for history of seizure disorder and who presented to Jackson Memorial Hospital for intermittent fevers and multiple unexplained bruises for 3 weeks as well as fatigue and weakness.The patient was recently started on valproic acid. Complete blood count (CBC) was obtained and showed a platelet count of 23 x10(3)/mcL with WBC of 3.5 x10(3)/mcL and hemoglobin of 9.7 g/dL.Serum valproate concentration was critically high (154 mg/L). Trephine biopsy showed a normocellular marrow (60%) showing maturing trilineage hematopoiesis and scattered atypical megakaryopoiesis characterized by small forms that are seen in relatively loose interstitial clusters (Figure 1). The marrow aspirate smears were characterized by cellular spicules with dysmegakaryopoiesis including numerous small hypolobated forms with frequent forms showing separated nuclei (Figure 2, 3, and 4). Blasts did not appear increased, comprising overall 1% of marrow cellularity. Karyotype studies revealed a normal female karyotype, 46, XX. FISH studies using probes commonly detected in MDS were negative. Next generation sequencing was negative for AML specific mutations including GATA1 and GATA2 mutations.

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

Conclusion
This case report highlights the significant hematologic adverse effects of valproic acid, specifically pancytopenia with dysmegakaryopoiesis, raising the clinical suspicion of potential myelodysplastic syndrome. Critically high level of valproic acid (154 mg/L) and normalization of CBC after the stoppage of the medication strongly suggests that valproic acid can cause severe bone marrow suppression and specific morphologic atypia in the megakaryocytic lineage thus introducing a potential diagnostic pitfall. Because the CBC returned to normal, bone marrow biopsy was not repeated.
Essential Thrombocytosis and Hepatocellular Carcinoma: A Mechanistic Challenge
Authors: Mohammed S 
Published: October 2021

Abstract

Introduction/Objective
Thrombocytosis has been reported in 8.2% of patients with Hepatocellular carcinoma [HCC] and has been attributed to increased Thrombopoietin [TPO] production by the tumor.

Methods/Case Report
We present a case of a 68-year-old male with a history of Hepatitis C and ethanol abuse presented with complaints of headache and chills. Imaging studies revealed a large mass in the liver [right lobe] suggesting an HCC of fibrolamellar type. His platelet count [PC] was 965 K/mcL. The serum AFP [Alpha feto protein] concentration was &gt;51,800 ng/ml. There was no evidence of metastatic disease and the patient was started on Capecitabine and radiation therapy targeting the liver mass. Lung metastasis became evident and Sorafenib was added. His PCs and AFP concentrations however continued decreasing to 306 K/mcL and 460.7 ng/ml respectively. His PC then increased to a peak of 1.32 million/mcL 10 months later. The molecular workup done at our reference lab was positive for CALR [Calreticulin] mutation. The patient was started on Hydroxyurea and his PC decreased to 323 K/mcL at the time of writing. His AFP has remained stable. This case illuminates the complicated relationship between HCC and thrombocytosis. The therapy directed against the HCC did decrease PC and AFP concentration in our case. The second wave of thrombocytosis led to the discovery of CALR mutation, and the patient was diagnosed with Essential Thrombocytosis [ET]. Treatment with Hydroxyurea again decreased the PC while AFP concentration was increased but stable. Thrombopoietin levels have remained stable for the patient after treatment with Hydroxyurea.

Results (if a Case Study enter NA)
NA

Conclusion
Although the question of which mechanism(or possibly both) was at work in this case cannot be resolved definitely, two points are worth noting. The first is that- the assumption that the thrombocytosis was related to the HCC delayed testing for mutations associated with Essential Thrombocytosis. The second is that the TPO assay that may have yielded useful information in sorting out the alternatives was not ordered early enough before starting hydroxyurea.
Carboxypeptidase A1 (CPA1) immunohistochemistry is highly sensitive and specific for acinar cell carcinoma (ACC) of the pancreas
Authors: Uhlig R , Clauditz T 
Published: October 2021

Abstract

Introduction/Objective
Introduction: Carboxypeptidase A1 (CPA1) is a zinc metalloprotease which is produced in pancreatic acinar cells and plays a role in cleaving C-terminal branched-chain and aromatic amino acids from dietary proteins. This study assessed the utility of immunohistochemical CPA1 staining for diagnosing pancreatic acinar cell carcinoma.

Methods/Case Report
Methods: A total of 15,680 tumor samples from 132 different tumor types and subtypes as well as 8 samples each of 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format.

Results (if a Case Study enter NA)
Results: CPA1 was strongly expressed in acinar cells of all normal pancreas samples but not in any other normal tissues. CPA1 immunostaining was detected in 100% of 11 pancreatic acinar cell carcinomas and one mixed acinar endocrine carcinoma (MAEC), but absent in 449 pancreatic ductal adenocarcinomas, 75 adenocarcinomas of the ampulla of Vater, and 11,739 other evaluable cancers from 128 different tumor entities. A weak to moderate diffuse staining of epithelial and stromal cells of cancer tissues immediately adjacent to non-neoplastic pancreatic acinar cells often occurred and was considered to be caused by diffusion of the highly abundant CPA1 from normal acinar cells that may have suffered some autolytic cell damage.

Conclusion
Our data show that CPA1 is a highly sensitive and largely specific marker for normal and neoplastic pancreatic acinar cells. CPA1 immunohistochemistry greatly facilitates the otherwise often difficult diagnosis of pancreatic acinar cell carcinoma.
A Retrospective Review of the Effect of COVID-19 Pandemic on Laboratory Utilization
Authors: Olayinka O , Odujoko O , Barasch S , Farley J , Woodruff C , Chan S 
Published: October 2021

Abstract

Introduction/Objective
We performed a retrospective analysis of test volumes in clinical pathology prior to and during the COVID-19 pandemic to better understand the impact of the pandemic on our laboratory utilization.

Methods/Case Report
The laboratory information system was queried for test order volume in 2019 and 2020 using Discern Analytics 2.0. Representative tests including C-reactive protein (CRP), D-dimer, fibrinogen, ferritin, lactate dehydrogenase (LDH), procalcitonin, prothrombin time (PT), point of care iSTAT blood gas analysis, ABO and Rhesus typing (ABORh), antibody screening, flow cytometry, and serum protein electrophoresis (SPEP). Data was analyzed using Microsoft Excel 2013.

Results (if a Case Study enter NA)
The data showed an increase in the number of tests ordered and verified in the in-patient setting. The increase was most substantial for D-dimer, CRP and LDH with a percentage increase of approximately 200% on each test from year 2019 to 2020. An increase of 73% and 57% was noted for ferritin and fibrinogen respectively. A slight decrease in volume was noted for tests ordered in the out-patient setting including SPEPs during the pandemic. There was no significant change in the number of orders verified for point of care ISTAT blood gas testing between 2019 and 2020. Procalcitonin test volume increased steadily from its implementation in May 2020 with a steep rise in test volume in November and December. A total of 75,295 SARS-CoV-2 molecular tests were ordered between March and December 2020 with approximately 80% of the orders being performed as a send- out test.

Conclusion
The COVID-19 pandemic has had a substantial impact on laboratory utilization with significant volume increases in tests that guide the management of hospitalized COVID-19 patients and slight decrease in tests ordered mostly in the outpatient setting. These results may help guide current and future decisions relating to laboratory operations during pandemics.
Optimizing Run Control Performance in Tissue-Based Biomarker Testing: Experience of an Industry-Based CAP/CLIA Laboratory
Authors: Feng J D , Tozzi D , Liddell J , Gleason M , Pestic-Dragovich L , ElGabry E 
Published: October 2021

Abstract

Introduction/Objective
Introduction: In contrast to traditional labs, our CAP/CLIA Lab performs patient sample testing only for pharma-sponsored clinical trials. Very limited patient material is received, usually in the form of unstained slides rather than wet tissues. Strict run control (RC) quality measures are therefore essential to avoid repeat testing, exhaustion of patient material and/or delay of patient enrollment decisions. We describe methods to optimize RC staining performance and consistency.

Methods/Case Report
Methods: The RC failure rate was evaluated retrospectively and prospectively from January 2018 through March 2021. Specific failure modes were evaluated, including: 1) instrument-related (catastrophic mechanical failure, slide derailment, low temperature error), 2) stain-related (lighter or darker staining vs. reference), 3) tissue-related (tissue loss/fall-off). RC failures were also tracked by instrument and by individual biomarker.

Results (if a Case Study enter NA)
Results: 33,189 patient samples (84,130 slides) were tested from January 2018 through March 2021. Concurrently, 14,794 RC slides were tested across more than 115 biomarkers, including immunohistochemistry, multiplex immunofluorescence, and in situ hybridization assays. The RC failure rates by year were: 2018: 3.2 % (116 RCs), 2019: 3.8% (156 RCs), 2020: 1.9% (100 RCs), and 2021 (through March) 1.3% (21 RCs). The decrease in RC failure rate was a direct result of process changes addressing each of the failure modes, including, but not limited to: 1) improvement in slide storage conditions, 2) more selective RC tissue selection, and 3) more consistent interaction with on-site instrument support.

Conclusion
Process improvements addressing pre-analytic and analytic RC failure modes have resulted in a year-over-year decrease in RC failures. Consequently, our first-pass rates for immunohistochemical, immunofluorescence multiplex, and in-situ hybridization testing of patient samples have increased. Close monitoring of RC failure rates and near-real-time troubleshooting of individual RC failures are important components of successful operation in our unique laboratory setting, where patient material for testing is limited.