bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next Generation Sequencing of Renal Medullary Carcinoma Diagnosed Concurrently with Sickle Cell Trait: A Case Report and Literature Review
Authors: McCool I , Dasgupta A , Jordan M 
Published: October 2020

Abstract

Casestudy
We present a 33-year-old African American male with 4 months of intermittent right flank pain and gross hematuria with hypermetabolic retroperitoneal lymphadenopathy, persistent right-sided hydronephrosis, perinephric fat stranding and a 5.5-cm hypermetabolic right lower pole mass demonstrated on imaging.

Results
Core needle biopsies of the mass contained atypical glands composed of epithelioid cells with pleomorphic nuclei, prominent nucleoli, eosinophilic cytoplasm and abundant mitoses infiltrating through desmoplastic stroma.
Immunohistochemical staining demonstrated CK7 and PAX8 reactivity of the tumor cells, and negative staining for CK20, WT1, PSA, PLAP and CD10. The patient underwent a radical right nephrectomy; microscopic examination illustrated invasion of the renal sinus, perirenal fat, and lymphovascular space by the neoplastic glands and sickling erythrocytes in the vasculature. Further IHC staining revealed intact mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) and a loss in expression of INI1 (SMARCB1), leading to the concurrent diagnoses of renal medullary carcinoma and sickle cell trait (confirmed with hemoglobin fractionation). Next generation sequencing of 144 clinically significant genes detected no mutations.

Conclusion
Renal medullary carcinoma is a rare, aggressive neoplasm that accounts for less than 0.5% of all renal cell carcinomas and presents at an advanced stage. Patients are usually young males who are of African or Mediterranean descent with comorbid sickling disease. Although loss of SMARCB1/INI-1 gene expression is associated with this neoplasm, no effective therapeutic targets have yet been established. Renal medullary carcinomas are usually resistant to chemotherapy and radiotherapy, making the identification of an immunotherapy target paramount. With a median survival of four months from diagnosis, additional genetic studies of these malignancies may identify an effective treatment option for renal medullary carcinoma.
Multifocal Pancreatic Neuroendocrine Neoplasms In Tuberous Sclerosis: A Rare Case
Authors: Jadhav N C , Gang D L 
Published: October 2020

Abstract
Casestudy: Pancreatic neuroendocrine neoplasms (PanNEN) are rare accounting for 2-5% of pancreatic tumors. Although mostly sporadic, 10-20% are associated with inherited syndromes, notably MEN-1, Von Hippel- Lindau disease, neurofibromatosis type 1, and tuberous sclerosis (TS). When compared to sporadic cases, PanNEN in hereditary syndromes occur at a younger age, are often multifocal, cystic, and may show characteristic microscopic patterns. TS is an autosomal dominant multi-system disorder with mutations involving TSC1 or TSC2 genes which function as tumor suppressors by inhibiting mTORC1 kinase. PanNEN is observed in 1.5-1.8% of patients with TS and no surveillance guidelines for the assessment of pancreatic lesions are established. Compared to other syndromes, PanNEN associated with TS are solitary. To our knowledge, only two cases of multifocal PanNEN in TS patients have been reported. We present a case of a 67-year-old gentleman with a history of TS also affecting two daughters. He presented to the emergency department with severe abdominal pain. Abdominal ultrasound suggested acute appendicitis and an incidental 2.0 cm solid lesion was noted in the head of the pancreas. Follow-up MRI revealed two additional non-cystic masses in the pancreatic tail. Endoscopic ultrasound-guided biopsy of a tail lesion revealed monomorphic tumor cells with stippled chromatin without cytologic atypia. Immunohistochemical staining was positive for synaptophysin and chromogranin. Ki-67 labelling index was under 1%. Diagnosis of a well-differentiated neuroendocrine tumor (G1) was made. The patient denied symptoms of the carcinoid syndrome and no biologically active hormones were detected. Gallium PET scan revealed multiple foci of radiotracer uptake throughout the pancreas in addition to those described on MRI. Although PanNEN are rare in TS, malignant behavior has been reported. This case reinforces the importance of early detection through active surveillance, especially as surgical options may be limited in multifocal disease.
Multiplex Assays of Luminex for Identification of COVID-19 Antibodies in Patient Serum: Performance Evaluation and Comparison to ELISA
Authors: Shapiro M S , Wang X , Mendu D R , Firpo A 
Published: October 2020

Abstract

Introduction/Objective
Mount Sinai Hospital has received emergency use authorization (EUA) from the FDA for Coronavirus Disease 2019 (COVID-19) antibody testing using ELISA. This serological assay detects and titrates the presence of circulating antibodies to COVID-19. Other platforms have aimed to achieve the credentials of the ELISA instrument, including the multiplex assays of Luminex. The platform is known to have a greater throughput (384 wells vs. 96 wells per microplate) and faster processing speed (8 hours vs. 17 hours).

Methods
Luminex utilizes beads that couple to the same COVID-19 antigens (mRBD and mSpike) which were utilized for the ELISA assay. The beads are read determining the mean fluorescence intensity (MFI). In order to compare the two methods, our study included 61 patients with COVID-19 at Mount Sinai Hospital, to screen and titrate their sera using Luminex, and to correspond the MFI values with the ELISA titers.

Results
The Luminex assay has achieved the same level of confidence as ELISA. The 61 patients, representing 30 negatives and 31 positives, are consistently identified as such on both platforms. Our data highlights 32% of patients with a low titer (&lt;1:160), 42% of patients with a high titer (1:160 ~ 1:320), and 26% of patients with a very high titer level (&gt;1:320). These titers correlated well with the MFI values. Based on a cutoff of 80,000 MFI, the sensitivity and specificity of the assay is 98% and 85%, respectively, with no overlapping of MFI between positive and negative results.

Conclusion
Overall, the study has demonstrated that the Luminex is a strong alternative for the ELISA platform. The Luminex highlights the broad dynamic range with no overlapping between positives and negatives. Migration from ELISA to Luminex, a platform with faster and greater throughput, is therefore, highly desirable.
A Challenging Case of A Myeloid Sarcoma Misdiagnosed as High Grade B-Cell Lymphoma
Authors: Herrmann A , Mai B , Elzamly S , Wahed A , Nguyen A , Chen L 
Published: October 2020

Abstract

Introduction/Objective
A 46-year-old female presented with severe back pain associated with progressive bilateral lower extremity weakness and paresthesia, urinary retention, and constipation. Computed tomography revealed a retroperitoneal mass encasing the right psoas muscle, obstructing the right kidney, and extending to the thoracolumbar region resulting in severe spinal compression. An epidural tumor resection was subsequently performed at an outside hospital.

Methods
Histological sections showed sheets of blastoid neoplastic cells with intermediate to large nuclei, irregular membranes, fine chromatin, and prominent nucleoli. Immunohistochemical stains showed that these cells were positive for CD43, CD79a (weak, focal), BCL2, C-MYC, and PAX5 (weak, focal) and negative for CD10, CD20, CD30, ALK1, BCL6, MUM1, and Tdt. The Ki-67 proliferation index was 75-80%. With this immunophenotype, this patient was diagnosed with a high grade B-cell lymphoma and transferred to our institution for further work-up. On review of the slides, further immunohistochemical testing was requested which revealed positivity for CD117 and myeloperoxidase (MPO).

Results
The overall morphological and immunophenotypical features are most compatible with myeloid sarcoma (MS) with aberrant expression of B-cell markers and this patient’s diagnosis was amended. Interestingly, the patient’s bone marrow examination only showed 2% myeloblasts with left shifted granulocytosis and concurrent fluorescence in situ hybridization (FISH) studies were negative.

Conclusion
A literature review showed that 40-50% of MS are misdiagnosed as lymphoma. MS can frequently stain with B-cell or T-cell markers, as seen in this case, which makes it challenging for an accurate diagnosis and sub- classification. In addition, our case is interesting in that there was only extramedullary presentation without bone marrow involvement. Typically, MS develops after the diagnosis of acute myeloid leukemia (AML) with an incidence of 3–5% after AML. It can also manifest de novo in healthy patients, who then go on to develop AML months to years later. Therefore, this patient will require close follow-up.
A Case of Enteropathy Associated T-Cell Lymphoma (EATL) with Aberrant Phenotype, CD8+, CD56+: From Diagnosis to Death
Authors: Clarke-Brodber A , Eldibany M , Victor T 
Published: October 2020

Abstract

Introduction/Objective
Enteropathy Associated T-Cell Lymphoma (EATL) is a rare and aggressive subtype of primary intestinal T cell lymphoma which occurs in patients with Celiac Disease (CD), most prevalent in the western world with an incidence rate of 0.22-1.9 cases per 100,000. The classic immophenotype of these neoplastic intestinal T cells show loss of CD8 and CD56. The adherence to gluten-free diet, markedly decreases the incidence of this complication.

Methods
The patient’s previous and current biopsies, autopsy and EMR were reviewed. The patient is 66-year female that was diagnosed with Celiac Disease in 2003 after duodenal biopsy showed features suggestive of CD with positive anti-endomysial IgA antibody serology. She presents currently with burning abdominal pain, with subsequent CT scan showing a mass in the small bowel with mid gut rotation and lesions in the lungs, liver and bladder.
Endoscopy showed multiple lesions extending from the hypopharynx to the large bowel, which on biopsy showed CD3+ lymphocytes expanding the lamina propria and infiltrating the crypt epithelium. Given the patient’s clinical history a diagnosis of EATL was made. The patient passed 5 days after diagnosis due to small bowel perforation.

Results
The initial duodenal biopsy showed villous blunting and increased intraepithelial lymphocytes. The biopsies of the gastrointestinal lesions show abnormal infiltrate of pleomorphic, intermediate in size lymphocytes with round to irregular and occasionally cleaved nuclei with pale to clear cytoplasm. These cells infiltrate the crypt epithelium. The immophenotype of these neoplastic cells are positive for CD3, CD7, CD8, CD56, TIA-1 and BF1, while negative for CD4, CD5 and CD30. T cell clonality was also positive. In addition to the above lesions, autopsy revealed involvement of an area of small bowel perforation with full-thickness mucosal wall involvement by the neoplastic cells. In addition, there is widely dissemenated disease involving the lung, liver, bone marrow, spleen, mesenteric lymph nodes, omentum, bladder, ovaries and myometrium (first report of uterine involvement).

Conclusion
CD8 positive EATL may occur in 19-30% of cases, and increases up to 50% in refractory CD. The differential diagnosis of MEITL, which is typically CD8 positive, is important and most be distinguished on the basis of clinical setting in the presence of Celiac Disease.
A Rare Case of Chronic Lymphoproliferative Disorder of NK Cells with an Unusual Expression of CD57
Authors: Laharwani H , Perrizo K , Jain S , Lam J 
Published: October 2020

Abstract

Introduction/Objective
Natural Killer cells (NK-cells) malignancies are extremely rare and the two NK-cell disorders involving the peripheral blood and bone marrow include chronic lymphoproliferative disorder of NK-cells (CLPDNK) and aggressive NK-cell leukemia (ANKL). ANKL is EBV associated with a prevalence in Asian adults and a fulminant clinical course leading to death within 2 months.

Methods
A 76-year-old female with a history of iron deficiency anemia presented for evaluation of lymphocytosis (78 TH/mm) and negative EBV with extreme fatigue, weight loss, and worsening weakness from the past 8 months.

Results
The peripheral and bone marrow aspirate showed an increase in granular lymphocytes with bland nuclei and abundant pale-staining cytoplasm containing fine to coarse azurophilic granules with no evidence of nuclear atypia. Flow cytometry demonstrated an atypical lymphocytic cell population comprising &gt;50% of total marrow and peripheral blood lymphocytes demonstrating loss of CD56 and diminished CD7 expression. The analysis showed atypical lymphocytes with the following immunophenotype: CD2, CD8 (the majority, at least 75%),CD7 (dim), CD38, CD11c (subset) with no expression of CD3, CD5, CD4, CD56, or CD11c. Flow cytometry is important as it helps in the phenotypic detection of aberrancy. A broad panel of immunohistochemical stains revealed scattered positivity for CD3, CD4, CD7, CD8, TIA-1, granzyme, perforin, and tryptase and negative for CD56 and CD57. Our top differential with a similar clinical course included T-cell large granular lymphocytic leukemia which is characterized by a clonal proliferation of mature cytotoxic T cells and also has an indolent course. They show CD3 positivity by flow cytometry along with co-expression of NK cell-associated markers (CD16 and CD57), and variable expression of other pan T cell markers such as CD2, CD5, CD7. It is found incidentally in patients having cytopenias with a persistent increase in circulating mature NK-cells. Of note, the PET scan revealed splenomegaly with no other significant findings.The patient was started on steroids and is currently doing well.

Conclusion
Thus, overall morphologic, immunophenotypic, and molecular results with negative expression of surface or cytoplasmic CD3 as well as the absence of TCR expression were most consistent with CLPD-NK with an unusual expression of CD57 expression detected in flow cytometry.
Coagulation Testing in Acute Ischemic Stroke Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants
Authors: Kamel Y S 
Published: October 2020

Abstract

Introduction/Objective
In patients who present with acute ischemic stroke while on treatment with non-vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke.

Methods
Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored.

Results
In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%-44% [95% confidence interval 1%-69%]). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients.

Conclusion
NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established.
Incidental Anaplastic Lymphoma in a Case of Herpetic Hepatitis
Authors: Perrizo K , laharwani H , Jain S , Lam J 
Published: October 2020

Abstract

Introduction/Objective
The role of Herpes Simplex Virus (HSV) virus in the development of lymphomas is unclear and poses a diagnostic challenge along with limited literature explaining the relationship between HSV and Anaplastic large-cell lymphoma (ALCL).

Methods
A 26-year-old female admitted for intractable fever (103.7 F), chills, and dysuria; her urine analysis was suggestive of a mild urinary tract infection. During the admission, she developed abdominal pain with subsequent CT- scan showing thickening of the gallbladder and possible cholecystic fluid. Her liver function tests were: albumin 2.8 g/dL, AST 394 U/L, ALT 303 U/L, ALP 156 U/L, total bilirubin 0.3 INR 1. A subsequent Magnetic Resonance Cholangiopancreatography (MRCP) showed heterogeneous enhancement pattern of the liver without any masses following which she underwent cholecystectomy, during which her liver was abnormal along with an enlarged peri- cholic lymph node. Intraoperative biopsy of the liver showed patchy hepatocyte necrosis and occasional hepatocytes with ground-glass nuclei. The morphologic features were suggestive for Herpes Simplex Virus (HSV) hepatitis, and an HSV immunohistochemical stain confirmed this diagnosis. Removal of the lymph node showed a sinusoidal infiltrate of atypical lymphohistiocytic cells with abundant pale cytoplasm and large moderately irregular nuclei and occasional prominent amphophilic nucleoli. A few “hallmark”-like cells with curved nuclei were noted with rare mitosis. A panel of adequately controlled immunohistochemical stains showed positivity for CD4, CD30 (variable), and CD45. CD2, CD3, CD5, CD7, CD8, CD10, CD15, CD20, CD68 (positive in adjacent macrophages), BCL2, ALK1 were negative.

Results
Flow cytometry was negative for a neoplastic leukocyte population with a polytypic B-cell population. Taken together, a diagnosis of ALK1 negative, ALCL was made. A subsequent CT scan revealed borderline enlarged para- aortic lymph nodes along with an increased number of non-enlarged lymph nodes in the bilateral axillary, mediastinal, lower neck, and subpectoral regions. A bone marrow biopsy performed was negative for lymphoma.

Conclusion
Off note, her hepatitis serology panel, CMV, and HIV screens were negative. Thus, with her unusual presenting symptoms and no signs of malignancy led to numerous workups, which further led to an infectious cause, however, the patient was ultimately discovered to have an occult ALCL.
Intracranial Hemorrhage In Patients Receiving Direct Oral Anticoagulant Therapy: Clinical Assessment, Management And Related Laboratory Studies
Authors: Xie M , Wyrzykowski M 
Published: October 2020

Abstract

Introduction/Objective
Direct oral anticoagulants (DOACs) have gained wide use in prevention and treatment of thromboembolic diseases. Although relatively rare with DOAC therapy, intracranial hemorrhage may become a medical emergency and needs to be managed with caution to avoid adverse consequences.

Methods
During the review of 94 patients with DOAC therapy related bleeding complications at William Beaumont hospital – Troy, Michigan, 3 patients were identified with intracranial hemorrhage. Information on DOAC therapy, the cause related to intracranial hemorrhage, and clinical assessment and management of these patients were collected from electronic medical charts with concurrent laboratory studies.

Results
There were 1 male and 2 female patients, ages 63, 67 and 86. Two patients were taking rivaroxaban 20 mg daily and 1 patient apixaban 5 mg bid for atrial fibrillation and DVT. Patients were clinically stable with no prior significant bleeding events, except for minor skin rashes. All patients experienced a minor trauma to the head and showed signs of brain injury. They were brought to the emergency department immediately. DOAC therapy was discontinued during the emergency evaluation. CT studies revealed 1 patient with subdural hematoma and 2 patients with focal intraparenchymal hemorrhage without mass effects. Both clinical and laboratory assessment revealed stable medical conditions. Patients received conservative care without surgical intervention and repeat CT studies demonstrated resolution of hemorrhage. One patient discontinued DOAC therapy permanently and the others resumed DOAC therapy with antidotes available. Clinical follow up showed no additional bleeding events.

Conclusion
Intracranial hemorrhage can occur in patients received DOAC therapy, even in clinically stable patients, and most likely happens after head injury. In this small group of patients, both clinical and laboratory evaluations showed stable medical conditions, with no need for surgery intervention. However, the decision of continuing DOAC therapy should be made with caution and it is reasonable to have antidote available for these patients.
Accuracy of the Criteria for Hemophagocytic Lymphohistiocytosis
Authors: Aksionau A , Wei E 
Published: October 2020

Abstract

Introduction/Objective
Regular assessment and analysis of diagnostic criteria for any type of human pathology is a prerequisite for ensuring the highest level of patient care. Hemophagocytic lymphohistiocytosis, also known as hemophagocytic syndrome, is a life-threatening condition. The syndrome can develop in critically ill patients with malignancies, severe infections, during chemotherapy, and may be associated with currently known genetic abnormalities, but this list is incomplete.
We draw attention to the accuracy of diagnostic criteria, association with a variety of clinical conditions, pathophysiological mechanisms, and outcomes of the disease.

Methods
From the medical records in our hospital, we were able to extract several cases over a 10-year period. Based on hemophagocytosis features, our list included 13 patients representing 11 bone marrow aspirates, 4 lymph node biopsies, 1 liver biopsy, and 1 spleen sample; repeated examination of the slides confirmed the accuracy.
Analyzing medical documentation, we evaluated the sequence and competence of the criteria used, the time required for diagnosis, management, and outcomes.

Results
We found that not all criteria were used for diagnosis, and the most sensitive and specific tests were bypassed. The preliminary diagnosis was made by a consultant (a rheumatologist or an oncologist-hematologist) on the 5th day of the hospital stay that delayed treatment. Of all the available treatment options, only a few were used.

Conclusion
The hemophagocytic syndrome is a very rare and fatal entity, it requires highly sensitive and specific diagnostic criteria for prompt diagnosis, targeted management, and thorough follow up. Every patient admitted to the hospital with a life-threatening condition should be suspected and tested for hemophagocytic syndrome on the first day. The criteria for hemophagocytic lymphohistiocytosis should be revised, with the most sensitive and specific ones are done in 100% of cases. Subsequently, each patient should be tested for the presence of genetic abnormalities that correlate with the syndrome.