bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key Considerations when Evaluating Whether to Establish a PD-L1 Laboratory Developed Test (LDT)
Authors: Hung Y , Liu X , Nam M , Rosa M , Saeed L , Schulte J J , Zhang H , Zhang W , Chivukula M , Beumer K , Kelly M , Kim J , Lazure P , Murray S 
Published: November 2023

Abstract

Introduction/Objective
Programmed death ligand-1 (PD-L1) immunohistochemistry (IHC) testing is often used to identify patients with cancer who may be eligible for immune checkpoint inhibitor therapy. The complexity around using different assays and platforms has caused confusion and reluctance to perform in-house PD-L1 testing. Some labs have established a laboratory developed test (LDT) that may be used across multiple types of tumors. To evaluate the role of PD-L1 LDTs, ASCP formed an ad-hoc working group to identify key considerations.

Methods/Case Report
In early 2023, 40 pathologists and laboratory professionals joined the ASCP PD-L1 Learning Collaborative to explore ways to improve PD-L1 testing processes. An ad-hoc working group focused on LDTs and reviewed the literature, spoke with labs using LDTs, and developed guidance questions.

Results (if a Case Study enter NA)
The working group identified these key topics and questions:
Testing volume and types of cancers: How many tests are performed each month to justify an in-house PD-L1 test? Which types of cancers are tested? Do we have (or do we plan to develop) reflex PD-L1 testing protocols for certain types of tumors?
Buy-in from oncologists: Do our medical oncologists feel that a PD-L1 LDT provides the results they need to make treatment decisions across different types of cancers?
Assay selection and testing platforms: Which IHC platform (eg, Ventana, Dako, Leica, etc.) do we currently use and which assay (eg, 22C3, 28-8, SP263, E1L3N, etc.) should we use? How well do these assays stain tumor cells vs. immune cells?
IHC testing processes: What is our volume of IHC testing and how would adding PD-L1 impact our workflow for all IHC tests? How often do we encounter technical issues? How much staff time will it take to add PD-L1? What are the maintenance costs?
Interpretation and scoring: Which pathologists are trained to interpret PD-L1 tests? Are they trained to interpret tumor cells, immune cells, or both? Do we train residents? Which scoring systems will we use and how will we report results?
Validation: How many cases are needed for validation? Should validation samples include tumor cell and immune cell staining?
Reimbursement: How will the lab be reimbursed for performing PD-L1 testing and interpretation?

Conclusion
Before establishing a PD-L1 LDT, the medical laboratory must review these questions against the backdrop of an evolving PD-L1 testing landscape. An LDT may be an appropriate approach for labs that aim to simplify PD-L1 testing based on the IHC platform(s) they are using.
Veteran Healthcare System: A Unique Healthcare Setting Providing Equitable Access to all Patients with Metastatic Lung Cancer in the Era of Precision Diagnostics
Authors: Dalal S , Petersen J M , Jhala D , Allbee A 
Published: November 2023

Abstract

Introduction/Objective
The National Comprehensive Cancer Network (NCCN) Non-Small Cell Lung Cancer (NSCLC) Guidelines Panel strongly advises broad molecular tumor profiling to identify mutations that help guide precision- based patient tailored therapy and subsequent patient counseling. Liquid biopsy with next generation sequencing represents a powerful tool to obtain this information through phlebotomy but is costly and only recently available.
Although ethnic minorities may not have the same access to health care resources, studies of ethnic access to liquid biopsies in the setting of Veteran patients at a Veteran Affairs Medical Center (VAMC) with metastatic lung cancer have not been well studied.

Methods/Case Report
A retrospective review was performed of all patients with a submitted liquid biopsy specimen at a VAMC and a history of metastatic lung cancer from November 26th, 2019, to March 3rd, 2023. Demographic data
was collected for each patient specimen and compared with the ethnic proportions noted in the census of the city where the VAMC is located.

Results (if a Case Study enter NA)
There were a total of 35 patient specimens, with the first liquid biopsy collection occurring on November 26th, 2019. The mean age of the patients was 70. The ethnic composition of the population was as follows: 16 were African American (45.7%), 16 were Caucasian American (45.7%), 2 mixed ethnicity (5.7%), and 1 declined to answer or were of unknown ethnicity (2.9%). The census of the surrounding metropolitan area demonstrated a general population ethnic composition of 43.6% African American and 44.4% Caucasian American.

Conclusion
The proportion of Veteran patients of each ethnicity with metastatic lung cancer that received liquid biopsy testing was similar to the ethnic distribution of the general population of the surrounding metropolitan area. This demonstrates that there was equitable access to this testing modality at the VAMC with potential to deliver best cancer care to the veterans by detection, prognosis, and monitoring treatment outcomes.
Primary Carcinosarcoma of the Pancreas with Focal Cartilaginous Differentiation
Authors: Mirzaei Baboli K , Salehiazar S , Mousavi S , Rector A R 
Published: November 2023

Abstract

Introduction/Objective
Carcinosarcoma is a neoplasm reported in multiple sites with a biphasic pattern sharing both sarcomatous and epithelial morphology. Each component should constitute 30% of the neoplasm to qualify as carcinosarcoma, according to the World Health Organization (WHO) classification. This subtype of malignancy is most frequently found in the uterus but carcinosarcoma of the pancreas is extremely rare. It is a very aggressive tumor with a low survival rate.

Methods/Case Report
A 76-year-old Caucasian man with a history of hypertension was admitted to the emergency department with new-onset atrial fibrillation and ischemic stroke 5 months ago. Initial workup showed "moth-eaten" lesions in the skull base and clivus bone, suggesting malignancy. The further evaluation led to chest/abdomen and pelvis CT scans, revealing a subtle attenuation in the pancreatic tail. MRI of the abdomen showed a pancreatic tail mass concerning pancreatic cancer. CA19-9 and CEA were elevated (133 U/ mL, and 10 ng/ mL, respectively).
Endoscopic ultrasound was performed and showed a 2 cm mass in the tail of the pancreas and fine needle aspiration (FNA) confirmed malignancy with a diagnosis of adenocarcinoma. The patient received neoadjuvant chemotherapy with gemcitabine and paclitaxel and underwent distal pancreatectomy, splenectomy, and left adrenalectomy.
Histopathologic examination revealed a biphasic neoplasm with moderately differentiated adenocarcinoma and abruptly transitioning spindle cell malignancy with focal cartilaginous differentiation. Due to the presence of focal cartilaginous differentiation, no immunohistochemistry (IHC) was required and a final diagnosis of carcinosarcoma of the pancreas with multiple lymph node involvement (ypT2, pN2) was made.

Results (if a Case Study enter NA)
NA

Conclusion
Carcinosarcoma is a neoplasm of mixed epithelial and mesenchymal-like tumor cells on pathologic examination. IHC is often very helpful for correct diagnosis, especially Cytokeratin and CEA. In this case, due to the presence of high-grade spindle cell sarcoma and cartilaginous differentiation, no IHC is required. Surgical resection is the definitive treatment for operable patients and is recommended when possible. In this case, only the adenocarcinoma component was identified preoperatively on FNA, and standard pancreatic adenocarcinoma neoadjuvant chemotherapy was also utilized in treatment.
Sepsis Inpatient Diagnostic Testing at Mid-Size Academic and Non-academic Health Systems
Authors: Zhou Y , Windham A K , Staker C , Whitted M , Brimhall B , Podichetty A , Clark K 
Published: November 2023

Abstract

Introduction/Objective
Comparison of clinical laboratory test and radiology imaging utilization for sepsis inpatients across multiple academic and non-academic health systems would be useful for healthcare resource utilization benchmarking.

Methods/Case Report
We compared laboratory and imaging utilization for adult patients hospitalized for sepsis procedures at mid-size (250-450 hospital beds), academic (N=12; 31,353 hospitalizations) and non-academic (N=18; 54,192 hospitalizations), hospitals using the Vizient Clinical Data Base™ over 3 years (2019-2021). We used Medicare Severity Diagnosis Related Groups (MSDRG), used by the US Centers for Medicare and Medicaid Services (CMS), to identify hospitalizations for sepsis (MSDRG triplet 870/871/872). We stratified patients by severity comorbid conditions and complications into high, moderate, and low severity groups. We compared the mean number of clinical laboratory (CPT codes 80000-89999) and imaging studies (CPT codes 70000-79999) per hospitalization and per hospital day. We also measured aggregate clinical Resource Intensity Weight (RIW) per hospitalization to quantify diagnostic resource consumption for each encounter. The RIW is based on the US Centers for Medicare and Medicaid Services (CMS) Ambulatory Payment Classification (APC) weights.

Results (if a Case Study enter NA)
Mean laboratory tests were significantly greater (p&lt;.01) at academic hospitals per encounter (152.2 vs. 95.4 tests, 59.5% higher) and per hospital day (14.5 vs. 9.9 tests, 46.5% higher). Laboratory RIW was also higher per hospitalization (21.0 vs. 13.5 RIW, 55.6% higher) and per hospital day (2.0 vs. 1.4 RIW, 42.9% higher) at academic hospitals. Mean imaging studies at academic hospitals were higher per case (7.8 vs. 7.2 studies, 8.3% higher) but not different per day (0.80 for both hospital groups). Imaging RIW was not significantly different between academic and non-academic hospitals either by encounter (11.1 vs. 9.9, 12.1% higher) or per day (1.2 for both hospital groups). Imaging comparisons lacked statistical significance. Analysis of utilization after stratification for severity levels revealed a similar pattern with greater differences in the high severity group.

Conclusion
Mean laboratory tests and laboratory RIW per hospitalization are greater at academic hospitals. These differences persist after adjustment for hospital length of stay and severity level. Differences in imaging studies and imaging RIW were not significant.
Atypical Teratoid Rhabdoid Tumor: 28-years institutional experience
Authors: Shaheen M , Vortmeyer A O 
Published: November 2023

Abstract

Introduction/Objective
Atypical teratoid/rhabdoid tumor (ATRT) is a malignant central nervous system tumor affecting young children, characterized by biallelic mutations of SMARCB1 (hSNF5/INI1), consisting of a varying mixture of rhabdoid cells, small round blue cell (SRBC) and epithelial/mesenchymal components. Combination of surgical resection, chemoradiotherapy and autologous stem cell transplantation (SCT) has led to significant improvement in survival.

Methods/Case Report
Cases of ATRT in the past 28 years have been re-examined, including H&E stains, immunohistochemistry, available molecular studies and clinical charts.

Results (if a Case Study enter NA)
A total of 23 cases of ATRT were recruited to include 20 pediatric (age 3-36 months, median 13.5 months) and 3 adult cases (27, 38 and 46 years). 73.9% were male. Two pediatric cases presented in patients with Pierre-Robin sequence and Phelan-McDermid syndrome and one adult had history of Choriocarcinoma. 72.7% of cases initially presented in the posterior fossa, with 3 cases presenting in temporal lobe, 1 in frontal lobe, 1 in 3rd ventricle and 1 in pituitary gland. Mean size at presentation was 4.7 cm (range 2-10 cm).
Median survival was 12.5 weeks with 8 patients surviving 5-13 years. 10/22 cases developed recurrences and/or spinal drop metastasis. Median time to first recurrence/ drop metastasis was 3.5 months (range 0-66 months). Cases showed varying proportions of rhabdoid, SRBC, epithelioid and mesenchymal components. By immunohistochemistry, INI1 was lost in 19/19 cases. Keratins, GFAP and Synaptophysin were positive in 13/17, 14/20 and 17/21 cases, respectively. Interestingly, GAB-1 and YAP1 were positive in 5/6 and 4/4 cases, respectively. Five cases had SMARCB1 mutation on NGS, one had NF2 truncation and another showed variation of unknown significance involving mainly NOTCH1 gene. 21/22 patients underwent surgical resection, of which 17 additionally received a combination of chemoradiotherapy and SCT and 1/22 underwent palliation.

Conclusion
Our data highlights the spectrum of presentation and survival of cases of ATRT and the importance of INI1 immunohistochemistry in the diagnosis, especially for the occasional cases co-expressing GAB1 and YAP, a potential diagnostic pitfall with medulloblastoma.
Case of Metastatic Atypical Meningioma to Lung: Utility of Cytological Preparations for Intraoperative Diagnosis
Authors: Guo Y , Valk J E , Fecher R , O'Toole K , Saqi A , Sonett J 
Published: November 2023

Abstract

Introduction/Objective
Meningiomas are the most common primary intracranial and intraspinal tumors. They are typically benign with an indolent behavior but can metastasize extracranially to the skin, bone, lymph node and liver. Lung metastasis is exceptionally rare, and the diagnosis can be challenging, especially during intraoperative diagnosis without ancillary studies. We describe a metastatic atypical meningioma to the lung for which intraoperative cytology facilitated the diagnosis and guided management.

Methods/Case Report
A 53-year-old woman with a history of left frontal atypical meningioma and multiple surgical resections for recurrences at outside hospitals, presented with an incidental left lung nodule. A lung wedge resection was performed and submitted for intraoperative diagnosis. Gross examination revealed a well-circumscribed, tan- white, and rubbery subpleural nodule. Cytological preparations— Diff-Quik and H&E stains—and frozen section were prepared.
Cytologically, the nodule displayed cohesive distinctive papillary whorls of uniform eosinophilic cells with indistinct cell membranes, round to oval nuclei with central nucleoli and intranuclear pseudoinclusions. The frozen section exhibited similar cytological features, few identifiable whorls and predominantly solid sheets of tumor cells typical of non-small cell carcinoma. Based primarily on the cytological findings, the intraoperative diagnosis was a neoplasm with papillary growth pattern, and a metastasis was favored based on the whorled pattern and clinical history; no further resection was performed.
Permanent sections displayed mitoses and no necrosis. Immunohistochemical analysis revealed positivity for somatostatin receptor 2a, progesterone receptor, and EMA (focal); no staining was seen with pancytokeratin, TTF-1, or p40. A diagnosis of atypical meningioma, WHO grade 2, was rendered. Subsequently, an atypical cranial and temporalis muscle meningioma at the site of the prior craniotomy bone flap was resected and had an identical molecular profile (1p36 deletion) to that in the lung, further supporting metastasis to the lung.

Results (if a Case Study enter NA)
NA

Conclusion
This case illustrates a rare presentation of metastatic atypical meningioma and highlights the distinctive intraoperative utility of cytology preparations—architectural and cytological details—for diagnosis and appropriate management. Cytology preparations can be a valuable tool and complement frozen sections, in which certain morphological features may be less obvious or confounded by freezing artifact.
Primary Chest Wall Ewing Sarcoma with Indolent Behavior in an Elderly Male
Authors: Sagan O , Schmidt A L , McMullen P 
Published: November 2023

Abstract

Introduction/Objective
Ewing sarcoma (ES) is the second most common primary malignant bone tumor, primarily affecting children and young adults within the first two decades of life. Over 80% of cases are positive for CD99 and exhibit a characteristic t(11;22) translocation resulting in an EWSR1::FLI1 fusion. Extraosseous ES is extremely rare and most reported cases occur in patients less than 50 years old. We report an unusual case of extraosseous ES arising from the chest wall in an elderly male that showed slow interval progression on imaging studies.

Methods/Case Report
An 83-year-old male with a past medical history of COPD and tobacco use presented to the emergency department for a mechanical ground level fall and a worsening cough over the prior week. Of note, he was found to have a 6.1 cm pleural based mass seven years prior. The patient was ultimately discharged home with recommended oncologic follow-up for this long-standing chest wall mass due to an increase in size on imaging. A PET scan showed a hypermetabolic subpleural mass in the right lower chest wall measuring 7.6 cm with invasion through the adjacent ribs and intercostal spaces into the adjacent soft tissue. A core biopsy was performed, which demonstrated a small round blue cell tumor diffusely positive for CD99 and Bcl-2, lacking significant mitotic activity and necrosis. Given the unusual clinical features, a next generation sequencing (NGS) panel for sarcoma fusions was performed and identified an EWSR1::FLI1 fusion, supporting the diagnosis of ES/primitive neuroectodermal tumor (PNET).

Results (if a Case Study enter NA)
NA

Conclusion
ES is relatively common as a primary bone tumor in children and young adults, but is rare in the chest wall and pleura and is extremely rare in the elderly. The clinical course for ES is typically aggressive. Diagnosis of ES can be challenging as CD99 positivity is nonspecific. The characteristic t(11;22) EWSR1::FLI1 fusion can be identified through FISH or NGS. At 83 years old, this is, to our knowledge, the oldest patient reported in the literature with this diagnosis. The slow interval growth of this mass over a period of seven years is also unusual. These combined clinicopathologic features are exceedingly unique and expand upon the reported spectrum and behavior of the Ewing’s family of sarcomas. The use of broad NGS panels among pathologists may result in increased identification of ES in unusual clinical settings in the future, while also providing more confident pathologic classification in challenging situations.
A diagnostically challenging case of Lymphoplasmacytic lymphoma involving the kidney clinically mimicking benign hypertension associated chronic kidney disease
Authors: George R S , Huang X , Lightle A 
Published: November 2023

Abstract

Introduction/Objective
Lymphomas involving the kidneys are under-recognized and often do not present clinically with signs and symptoms raising suspicion for a hematological malignancy. Worsening renal function may necessitate renal biopsy, but often the clinical picture may not warrant a biopsy. We herein present a case of lymphoplasmacytic lymphoma involving the kidney clinically mimicking benign renal vascular disease associated chronic kidney disease.

Methods/Case Report
Elderly male with past medical history of stage 3 chronic kidney disease presumed to be due to benign hypertension and undergoing treatment for the same presented to his nephrologist for routine follow up. His renal parameters were stable, but his high blood pressure seemed to be difficult to control despite maximum medical intervention. Upon the patient’s request to know exact etiology of his kidney problem, a renal biopsy was performed. Histomorphological evaluation revealed multifocal areas of renal parenchymal infiltration by atypical lymphocytic aggregates with background renal parenchyma showing moderate arteriosclerosis, mild interstitial fibrosis, tubular atrophy and no significant glomerulopathy. Further workup of the lymphoid aggregates led to the finding of a low grade CD5 negative, CD10 negative B-cell lymphoma with plasmacytic differentiation. Molecular testing for final characterization revealed a MYD88 mutation, which along with the immunomorphological findings confirmed the diagnosis of lymphoplasmacytic lymphoma (LPL). The patient was referred to hematology-oncology and was recommended to start chemotherapy due to renal involvement.

Results (if a Case Study enter NA)
n/a

Conclusion
In medical renal biopsies, lymphocytic infiltrates in areas of interstitial fibrosis are very common, and an atypical lymphocytic infiltrate can be easily overlooked. Pathologists evaluating these biopsies should have a high degree of suspicion for a hematological malignancy if they encounter atypical lymphocytic infiltrates in the renal parenchyma. Accurate diagnosis is essential, as renal lymphoma whether primary or metastatic, requires initiation of timely systemic chemotherapy.
Blood Type Verification Rejection Rate Reduction
Authors: Abdelmonem M , Cai W , Kilambi S , Yoshizuka S , Nguyen A , Quach T , Howard E , Chang S , Vukic K , Shan H , Yunce M 
Published: November 2023

Abstract

Introduction/Objective
Specimen collection is an initial pre-analytical process that ensures accurate, reliable, and timely patient results. In accordance with AABB and CAP Standards, Transfusion Service rejects specimens if they do not meet predefined technical requirements for each specific analyte. First-time patients admitted to Stanford Health Care (SHC), requiring blood transfusions, must have a current blood type on file. The blood type must be confirmed with a second, independent blood specimen called the Blood Type Verification (BTVI). Collection of the BTVI ensures that the patient’s blood type is confirmed. This is required in order to help prevent transfusion of ABO-incompatible blood products, which could result in a potentially severe transfusion reaction. SHC policy requires the Type and Screen (TNS) and BTVI to be drawn at least one minute apart. If collected at the same time, the BTVI specimen is rejected a and a redraw is requested. This process could potentially delay patient care and cause patient discomfort.

Methods/Case Report
It was identified that a key component to decrease specimen rejections would be to leverage technology to drive adherence to policy, rather than rely on human-driven, manual processes. In collaboration with Nursing and IT, a technological mechanism was developed to disallow the printing of the BTVI label until the TNS is documented as collected within the electronic health record (EHR). The BTVI would be accessible one minute after the TNS is collected to ensure that a second, independent patient verification is completed. The IT solution ensures that the documentation time follows policy and standards, which, enhances patient safety by reminding staff to complete a second patient verification as needed

Results (if a Case Study enter NA)
We implemented the IT solution for BTVI in October 2022. The BTVI rejection rate for samples accounted for 52% of overall rejected specimens in the department. In October, November, and December, the BTVI sample rejection rate accounted for 47%, 10%, and 0% of overall rejected samples in the department, respectively. We continue to monitor BTVI rejection rates closely to ensure that the IT solution is working as expected and that standard workflow is followed per SHC policy

Conclusion
This IT enhancement has improved patient safety by ensuring that accurate blood type is determined to provide cross- matched blood products to patients in a timely manner. Additionally,, it has improved patient care by reducing the number of redraws and preventing transfusion delays.