bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Cell mRNA Sequencing of Murine and Human Alopecia Areata Identifies Immune Cell Profiles Predictive of Human Disease State
Authors: Borcherding Nicholas , Crotts Sydney , Ortolan Luana , Bormann Nicholas , Jabbari Ali 
Published: October 2020

Abstract
Alopecia areata (AA) is one of the most common autoimmune conditions, presenting initially with loss of hair without overt skin changes. The unremarkable appearance of the skin surface contrasts with the complex immune activity occurring at the hair follicle. AA pathogenesis is due to the loss of immune privilege of the hair follicle leading to autoimmune attack. Although the literature has focused on CD8+ T cells, vital roles for CD4+ T cells and antigen-presenting cells have been suggested. Here, we use single-cell mRNA sequencing to reveal distinct expression profiles of immune cells in AA. We found clonal expansions of both CD4+ and CD8+ T cells, with shared clonotypes across varied transcriptional states. Demonstrating distinct gene and clonotypic variations, AA murine data were used to generate highly predictive models of human AA disease. In order to corroborate the results, single-cell sequencing of T cells in human AA recapitulated the clonotypic findings and the gene expression of the predictive models. Taken together, this work demonstrates the unique transcriptomic environment of AA skin, not just limited to CD8+ T cells. This work also represents the first single-cell sequencing for the autoimmune condition AA.
Establishing a Nucleated Count Reflex Trigger for Performing Cell Differential on Cerebrospinal Fluid in Pediatric Patients
Authors: Abro Brooj , Jackups Ronald 
Published: October 2020

Abstract

Introduction
Analysis of cerebrospinal fluid (CSF) assists in the diagnosis of several disease processes affecting the central nervous system (CNS). Nucleated cell (NC) count and cell differential are two important components of laboratory testing performed to analyze CSF samples. These tests can help diagnose conditions such as infection, inflammation, and malignancy involving the CNS; however, the cell differential, performed manually on a cytospin, is labor-intensive and may divert laboratory resources. Currently, the laboratory at our tertiary care pediatric hospital performs both NC count and cell differential on all specimens submitted for CSF cell count analysis. We hypothesized that when the NC count is low (&lt;10/mcl), performing manual cell differential does not provide clinically meaningful information and leads to unnecessary testing, increasing the turnaround time and decreasing precision. In this study, we investigated the utility of performing a manual differential on CSF when the NC count is ≤10/mcl and the need to establish reflex criteria for performing a cell differential.

Methods
Data were extracted from our electronic medical record database. We searched for all CSF samples that were submitted to our pediatric hospital’s laboratory for cell count analysis from September 2019 to January 2020. NC count, red blood cell (RBC) count, and number of cells available for differential (€œcells diffed) on cytospin, to a maximum of 100 cells per specimen, were obtained for each sample.

Results
A total of 577 CSF samples from 332 patients were submitted and analyzed for cell counts, of which 471 (82%) had NC count ≤10/mcl. There was a significant moderate positive correlation between NC count and cells diffed (Pearson correlation coefficient, 0.45, P-value &lt;0.001). Of these 471 samples, 24 (5%) showed evidence of peripheral blood contamination (&gt;500/mcl RBCs in samples with NC = 0/mcl, &gt;500 x (NC count)/mcl RBCs in samples with NC &gt; 0/mcl). A total of 4 cases from two patients with NC ≤10/mcl (0.8%) showed blasts on manual differential. Both patients had B-lymphoblastic leukemia/lymphoma and were being evaluated for CNS involvement with concurrent cytology. One patient was diagnosed as negative for CNS involvement by cytology. The sample for manual differential was contaminated by peripheral blood, hence the presence of blasts did not represent CNS disease. The second patient had the remaining 3 positive samples and was diagnosed with CNS involvement by cytology on multiple follow-ups.

Conclusion
Performing CSF manual differential when NC &lt; 10/mcl does not provide additional clinically actionable information and is associated with a lower cell yield on the cytospin. Establishing a NC count cutoff for performing manual differential will prevent unnecessary testing, decrease turnaround time, and increase precision. Exceptions may be necessary for oncology patients at high risk for CNS involvement.
A Unique Presentation of Cryptococcus neoformans and Pneumocystis jirovecii (PJP) Co-Infection in a Newly Diagnosed HIV Patient
Authors: Zia Shereen , Tariq Zain , Schultz Daniel , Brar Indira , Tibbetts Robert 
Published: October 2020

Abstract
One week prior to demise, a 30 years old smoker male with a past medical history significant for intermittent asthma presented to emergency with shortness of breath, wheezing, productive cough, and generalized fatigue for 1 week. He was afebrile, normotensive, tachycardic and had O2 saturation of 96% on room air. Physical examination showed cachexia, audible wheezes and oropharyngeal erythema. Labs showed WBC 3600/uL with lymphocyte count of 700/uL and mild thrombocytopenia. Chest X ray was clear. Serology was reactive for HIV, pending viral load. Working diagnosis was asthma exacerbation in the setting of a possible viral infection for which he was discharged home to complete a 5-day course of high dose prednisone, with follow up with infectious diseases as an outpatient. Subsequent, HIV viral load after discharge was 194,643 copies/mL.
One week later, he presented to the ED with worsening respiratory symptoms, new onset chest pain and vomiting. He was hypotensive, tachycardic, tachypneic, and afebrile. He had leukocytosis of 12,700/uL with neutrophilia, lactate of 6.6, BNP 841. Influenza A, B and RSV, and urine histoplasma antigen were negative. EKG showed abnormal ST segment elevation with concerns for STEMI. Chest CT revealed multifocal, bilateral ground glass and nodular opacities with cystic cavities. Mediastinal and hilar lymphadenopathy was also noted. Pulmonary embolism and pneumothorax were ruled out. Blood gases reflected acute hypoxemic respiratory failure. Vancomycin and Piperacillin/tazobactam were started. A bed side ultrasound showed significantly dilated right ventricle with severely reduced function and hence concerns for cardiogenic component of shock. He was intubated and shortly after developed asystole and expired after prolonged cardiopulmonary resuscitation within twelve hours of admission.
At autopsy, gross exam showed bilateral pulmonary congestion, bilateral hilar adenopathy and matted lymph nodes in the mediastinum. Microscopy revealed cryptococcus (mucicarmine positive encapsulated yeast forms) involving intraalveolar and alveolar septal parts of all lobes of the lungs, effacing lymph nodes, and involving microscopic foci in bilateral myocardial ventricles. Modified GMS-positive cup shaped Pneumocystis organisms involved the alveolar spaces of all lung lobes. The lung parenchyma showed minimal inflammatory response.
Our case is of an HIV patient with respiratory symptoms found to have pulmonary co-infection with PJP and Cryptococcus neoformans, confirmed on pathology report. This is uncommon in literature. Additionally, this case is unique in reporting the presentation of Cryptococcus neoformans as involving the mediastinal lymph nodes and myocardium.
Primary Clear Cell Sarcoma of the Breast: A Case Report
Authors: Aldrees R , Wei S , Prieto-Granada C , Patel C 
Published: October 2020

Abstract
Casestudy: Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, is a primary soft tissue neoplasm exhibiting evidence of melanocytic differentiation. It is an uncommon aggressive tumor that arises in tendons and aponeuroses of the distal extremities. Here, we report the first case of primary CCS of the breast.
The patient was a 43-year-old female who presented with a left breast mass and underwent surgical resection at an outside hospital. No history of melanoma or any other malignancies was reported. Grossly, it was described as a 2 x 1.5 x 1.5 cm, well-demarcated, white nodular mass. Microscopic examination showed a malignant neoplasm composed of short spindle cells with ill-defined, eosinophilic cytoplasm and ovoid nuclei with finely stippled chromatin and exhibiting moderate pleomorphism. The lesional cells were arranged in short interlacing fascicles with abundant collagen, with brisk mitotic activity (&gt;15/10 HPF). The differential diagnosis included spindle cell carcinoma, myoepithelial carcinoma and melanocytic neoplasm. The tumor cells were immunoreactive for S-100 protein, SOX10, Mart-1, HMB45 and MiTF, but negative for multiple cytokeratins (including high and low molecular weight keratins), p63, EMA, CEA, Caldesmon, smooth muscle myosin, calponin, desmin, ERG, and CD31, thus confirming melanocytic origin. EWSR1 gene rearrangement was detected by fluorescence in situ hybridization analysis using break-apart probes. Overall, the histomorphology combined with the immunophenotype and cytogenetic characteristics, was most consistent with a CCS. To our knowledge, no primary CCS of the breast has been previously reported in the English language literature.
Clear Cell Sarcoma of the Premaxillary Soft Tissue: A Case Report
Authors: Tucker C M , Liu J , Gargano S M , Fundakowski C E 
Published: October 2020

Abstract
Casestudy: Clear cell sarcoma of soft tissue (CCSST) is a rare translocation-associated sarcoma which uncommonly presents in the head and neck region. Because the tumor expresses markers of melanocytic differentiation, it can be difficult to distinguish from malignant melanoma and epithelioid malignant peripheral nerve sheath tumor (MPNST), necessitating clinical correlation and ancillary testing specifically fluorescence in situ hybridization (FISH) for EWSR1 rearrangement. Here we report a case of CCSST involving the premaxillary soft tissue. A 61-year-old male without significant past medical history presented with a right premaxillary subcutaneous mass which was slowly enlarging over the course of three years. During surgical resection of the mass, the infraorbital nerve was noted to course into the tumor. Histologic sections revealed a 2.5 cm mass composed of a nodular proliferation of epithelioid tumor cells with pale eosinophilic to vacuolated cytoplasm, large vesicular nuclei with prominent nucleoli, areas of punctate necrosis, and a mitotic rate of 10 mitoses per 10 high power fields. Scattered multinucleated tumor giant cells were also present. No pigment was identified. By immunohistochemistry, the tumor cells were diffusely positive for SOX-10 and S-100 and negative for HMB45, MART1, MITF, inhibin, calretinin, p63 and smooth muscle actin. FISH was positive for EWSR1 rearrangement. Altogether, the morphologic, immunohistochemical and cytogenetic findings supported the diagnosis of CCSST. Because the surgical margins were negative for malignancy, the patient did not require additional surgery but will be receiving adjuvant radiation therapy. Although rare in the head and neck, CCSST should be considered in the differential diagnosis when dealing with an epithelioid soft tissue tumor that expresses any melanocytic markers, and a definitive distinction from malignant melanoma and epithelioid MPNST can be achieved by utilizing FISH for EWSR1 rearrangement.
Paraganglioma of the Urinary Bladder Metastatic to the Lung in a Patient with SDHB Gene Mutation: A Case Report
Authors: Onyenekwu C P , Iczkowski K A , Sheinin Y 
Published: October 2020

Abstract

Introduction/Objective
Paragangliomas are tumors originating from the neural crest. Most tumors are benign and arise from various locations in the body. Extra-adrenal paragangliomas arise as sporadic cases in most settings or as part of heredofamilial syndromes in about one-quarter of cases. Succinate dehydrogenase subunit B (SDHB) gene mutations are associated with an aggressive clinical disease course of pheochromocytoma/paraganglioma.

Methods
We present a 41-year-old male former smoker with a history of a growing right upper lung nodule on chest imaging. He had no cough or respiratory symptoms. Twenty-seven months prior the patient underwent a cystoprostatectomy due to paraganglioma of the bladder. Genetic testing identified a pathogenic mutation in SDHB gene, c.166_170delCCTCA (p.Pro56Tyrfs*5). He underwent a wedge resection of the lung nodule.

Results
Sectioning of the lung wedge revealed a well circumscribed, firm tan nodule. Microscopically there were nests of large neoplastic cells with round nuclei and eosinophilic granular cytoplasm. Tumor cells were positive for synaptophysin and chromogranin and negative for pan-cytokeratin. S100 highlighted sustentacular cells. The pulmonary neoplasm was morphologically similar to the prior tumor of the bladder. These features are consistent with a metastatic urothelial paraganglioma to the lung, in a background of a hereditary paraganglioma syndrome.

Conclusion
Extra-adrenal paraganglioma occurring in a setting of hereditary paraganglioma syndrome has a higher risk of metastasis. Lifelong surveillance even after prompt resection of primary tumor with negative margins is required to ensure early detection of metastasis and prevention of complications associated with it.
A Comparative Analysis of Immunohistochemical Profile of Primary and Metastatic Endometrial Endometrioid Carcinoma
Authors: Xu K , Ye Q , Han L , Zhong M 
Published: October 2020

Abstract

Introduction/Objective
Beta catenin plays an important role in cancer tumorigenesis and have been found to be associated with metastasis in a variety of tumors. Analyzing TCGA data, we found that 30% of endometrial endometrioid carcinoma cases have beta-catenin mutations. We hypothesize that beta-catenin mutation may be associated with metastasis of endometrial endometrioid carcinoma. ER and PR expression was also compared to determine any changes after metastasis.

Methods
Retrospective institutional review of all endometrial endometrioid carcinoma (192 cases) between 2011 to 2018 was performed, including 149 cases of FIGO grade I, 38 cases of FIGO grade II and 5 cases of FIGO grade III. 19 cases with paired primary and metastatic specimen were identified. Immunohistochemistry staining (IHC) was carried out for ER, PR and beta-catenin.

Results
Median patient age was 56 years. The most common metastatic site was vagina, accounting for 68% of metastasis (14/19), followed by bladder (3/19), lung (2/19) and rectum (1/19). The primary and metastatic carcinoma of all 19 cases exhibit very similar morphology. All of those cases were positive and concordant for ER and PR in primary and metastatic endometrioid carcinoma. On the other hand, nuclear beta-catenin staining caused by mutation was positive in 5 metastatic carcinoma but not in primary carcinoma.

Conclusion
IHC expression of ER and PR remains unchanged between primary and metastatic carcinoma, demonstrating the reliability of ER and PR to confirm the origin of metastatic carcinoma. 26% of the metastatic carcinoma (5/19) exhibit nuclear beta-catenin staining but not in primary carcinoma, suggesting the possible role of beta-catenin in metastasis of endometrial endometrioid carcinoma.
Ossifying Fibroma of the Mandible – Benign Tumor with Aggressive Presentation
Authors: Siatecka H , Gannon F H , Rosen D G 
Published: October 2020

Abstract

Introduction/Objective
Ossifying fibromas are rare benign fibro-osseous lesions of mesenchymal origin affecting the craniofacial bones. Less than 60 cases have been reported in the literature. These tumors are more commonly seen in women and are usually slow growing. Most lesions are incidental, small and treated with curettage or enucleation. Rarely, ossifying fibromas can show a rapidly growing aggressive course that require radical resection.

Methods
We present a case of a 63-year-old man who presented with an enlarging left mandible lesion that was first noticed two years prior. We discuss the clinical presentation, prognostic factors and management of this rare disease based on the current literature.

Results
The patient presented with a left mandible mass that had recently grown, caused significant pain and affected chewing. The computed tomography showed a heterogeneous sclerotic lesion with periosteal reaction of the left mandible, but no evident mass. Initial biopsy showed a bland spindle cell proliferation admixed with fragments of woven bone. Due to clinical presentation the patient underwent left hemimandibulectomy with left neck dissection. The gross examination revealed 3 x 1.5 x 0.8 cm tan-pink tumor located at the junction of the mandible body and ramus, abutting the outer bone surface. Microscopic examination showed various shaped spicules of woven bone lined by osteoblasts in a vascularized, cellular, fibroblastic and spindled cell stroma consistent with aggressive ossifying fibroma. The tumor extended into the anterior and posterior bone resection margins. All the examined lymph nodes were negative for malignancy. No adjuvant radiation or other treatment was administered. The patient is alive without evidence of disease after 7 months of follow up.

Conclusion
The ossifying fibroma is a rare benign fibro-osseous tumor that can rarely have an aggressive behavior. Clinical, imaging and histopathological correlation are crucial to establish the correct diagnosis. Aggressive ossifying fibromas may require radical resection to prevent recurrence.
Rare Surgical Lung Biopsy Findings of Metastatic Pulmonary Calcification Associated with Chronic Renal Failure
Authors: Ronen N , Sheinin Y 
Published: October 2020

Abstract

Introduction/Objective
Metastatic pulmonary calcification is a metabolic lung disease characterized by depositions of calcium in lung parenchyma. Depositions of calcium salts are usually caused by hypercalcemia and are associated with end-stage renal disease, primary and secondary hyperparathyroidism, and hemodialysis. It is mostly asymptomatic and clinically silent but can lead to life-threatening respiratory failure.

Methods
We present a case of a 53-year-old woman, with a failed renal transplant and on hemodialysis, admitted with cough and shortness of breath. Computed tomography showed extensive diffuse bilateral groundglass and nodular opacities. Bronchoscopy was unremarkable. BAL results were negative for infection. The initial differential diagnosis included pneumonitis, interstitial lung disease, and chronic obstructive pulmonary disease. VATS lung wedge resection was performed.

Results
Microscopically there were numerous interstitial, peribronchial and perivascular calcifications highlighted by Van Kossa stain. Calcifications were associated with a marked interstitial fibrosis confirmed by trichrome stain. There was no evidence of significant acute and chronic inflammation, granulomas, fibroblastic foci and vasculitis.

Conclusion
Metastatic pulmonary calcification is found in 60–80% of autopsies of patients undergoing dialysis treatment. It is rarely diagnosed during their lifetime, because patients are usually asymptomatic, or the imaging findings are negative. The diagnosis of metastatic pulmonary calcification in our patient prompt further evaluation for repeat kidney transplant and the patient is being considered for parathyroidectomy for her tertiary hyperparathyroidism.
A Rare Case of Dedifferentiated Solitary Fibrous Tumor
Authors: Kanteti A P , Martinez Duarte E 
Published: October 2020

Abstract
Casestudy: Dedifferentiated solitary fibrous tumor is a rare malignant subtype of the common benign mesenchymal neoplasm with fibroblastic differentiation known as solitary fibrous tumor (SFT). These account for less than 2% of all soft masses; and about 20% of SFTs turn aggressive. They feature bland spindle cells creating a classic “pattern-less pattern” in collagenous stroma with prominent staghorn vessels. They can dedifferentiate into a biphasic tumor with low grade areas that are spindle cell rich and high-grade areas with epithelioid cells, mitotic figures and necrosis.
Here we present an 84-year-old female who came from an outside institution for a pathology review. The patient’s clinical history was lacking and biopsies from the right lower and middle lobes of the lung, azygous and hilar lymph nodes were investigated. The pathology revealed multiple areas with epithelioid cells that were pleomorphic and had high nuclear to cytoplasmic ratio. These areas also contained numerous mitotic figures, necrosis and giant cells; with lymphovascular space invasion. There was a clear demarcation between the epithelioid area and an area rich in spindle cells. The spindled areas revealed a fascicular architecture with intervening sclerotic stoma and prominent rounded and dilated blood vessels. Immunohistochemistry analysis of the epithelioid and spindle cell areas were positive for STAT6. Additional testing for CD34 was diffusely positive in the spindle cell component and only focally positive in the high-grade portion of the tumor. Ki-67stain was utilized to estimate the proliferative index which was up to 80 percent in the high-grade epithelioid component and about 15% in the spindle cell portion. These morphological and histochemical findings were consistent with the diagnosis of a dedifferentiated solitary fibrous tumor.
Pulmonary Hamartoma, A Relatively Common Diagnosis with a Rare Presentation
Authors: Sandeep F , Kaur G , Olayinka O , Sieber S , Pathan N 
Published: October 2020

Abstract
Casestudy: Pulmonary hamartomas (PH) are the most common benign tumors of lung, accounting for 75% of all the benign tumors and 8% of all the pulmonary neoplasms. These lung tumors are generally solitary and are observed in middle-aged and older adults with the peak incidence during the sixth decade of life. PH presents as asymptomatic nodule, found incidentally on routine radiographs and CT scans. The majority of PH are located in the lung parenchyma. Endobronchial hamartomas occur much less frequently. An extremely rare presentation of Hamartoma as a mediastinal mass is also reported in the past. The present article reports a case of a 72-year-old female, presented to her primary care physician with the complains of right lower abdominal pain. CT scan of the abdomen and pelvis revealed a partially visualized right paracardiac /mediastinal lipomatous mass. Patient stated that she was informed about a pericardial cyst of about golf ball size, noticed on a routine radiograph 40 years ago. Further workup with CT chest angiography revealed an 8.6 x 5.6 x 5.6 cm mediastinal mass associated with the right heart border and the right cardiophrenic angle, abutting the right diaphragm as well as the medial pleural reflection. A differential diagnosis of teratoma, lipoma/liposarcoma, and hamartoma was considered. Patient underwent robotic assisted surgical resection of the mass which emanated from right lower lung lobe. The histologic features and immunoreactivity pattern were consistent with a benign pulmonary hamartoma. Approximately 90 percent of PH presents as a peripheral intraparenchymal nodule whereas endobronchial hamartoma occurs much less frequently and represents 1.4% - 10 % of PH. A few cases of pulmonary hamartomas presenting as a mediastinal mass have been reported in the past few decades. Here in we report such a case of pulmonary hamartoma presenting as a mediastinal mass.