bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discordant Microsatellite Instability Status in Metachronous Primary Rectal Cancer Detected During IdyllaTM Microsatellite Instability Test Validation: A Case Report
Authors: Syriac S , Bauer L J , Mumtaz M 
Published: October 2024

Abstract

Introduction/Objective
Defects in DNA mismatch repair (MMR) can be identified by immunohistochemistry (IHC) MMR, Microsatellite Instability (MSI) status testing by PCR or by MSI testing by NGS. Discrepancies may occur between the different test methods. We describe a case of a discrepancy discovered during validation of an in-house IdyllaTM MSI test (PCR method), in which repeat testing by the external reference lab led to a definitive deficient MMR/MSI-High (MSI-H) status.

Methods/Case Report
A 67-year-old male presented with a new rectal mass on a follow-up colonoscopy. His past surgical history included a colorectal anastomosis secondary to a low anterior resection for pT3N0 upper rectal cancer ten years ago. He had a strong family history of colorectal cancer with his father, 3 brothers, 3 paternal uncles and 2 cousins affected.
Colonoscopy revealed an adenocarcinoma 3 cm distal to the anastomosis. MRI showed a plaque-like mucosal thickening along the remaining rectum below the anastomosis. He underwent a complicated redo low anterior resection. Histopathology revealed a pT1N0 invasive moderately differentiated midrectal adenocarcinoma.
Test results for an external PCR-based MSI test were microsatellite stable (MSS). However, repeat testing (requested after MSI-H status was detected by the in-house IdyllaTM MSI assay) revealed a deficient MMR status (loss of expression of MSH2 and MSH6 proteins) and MSI-H by PCR analysis. These discrepant results may have been due to low tumor cellularity and tumor heterogeneity (ie, heterogeneous pattern of MSH2/MSH6 loss on IHC).

Results (if a Case Study enter NA)
NA

Conclusion
Discrepancies in deficient MMR/MSI status between and within different test methods may be attributable to intratumoral heterogeneity and low tumor cellularity. In discordant cases, pathologists must not hesitate to perform a repeat analysis using alternate methods, as a deficient MMR/MSI-H diagnosis has crucial diagnostic, prognostic and predictive implications.
A Frozen Tale of Two Tumors in the Pancreas: An Intraoperative Diagnostic Challenge of Clear Cell Pancreatic Neuroendocrine Tumor Mimicking Metastatic Clear Cell Renal Cell Carcinoma
Authors: Fortes P , Daley S K , Wang H L , French S W 
Published: October 2024

Abstract

Introduction/Objective
Clear cell pancreatic neuroendocrine tumor (PanNET) is rare, with very few cases reported in the literature, and is often found in patients with von Hippel-Lindau (VHL) disease. The differential for this entity includes ectopic adrenal tissue and metastatic clear cell neoplasms. These challenges during intraoperative consultation add to the complexity of diagnosing this condition. Distinguishing it from other pancreatic lesions requires careful examination and further ancillary testing.

Methods/Case Report
We report a case of clear cell PanNET mimicking metastatic clear cell renal cell carcinoma (RCC) in a 56-year-old woman with recently diagnosed VHL. She presented with renal masses and a pancreatic lesion with previous biopsy showing conventional NET. Intraoperative consultation during her pancreaticoduodenectomy identified a 1.3 cm well-circumscribed, golden-yellow solid mass. Further characterization was deferred to permanent sections given the diagnostic challenge of distinguishing between a PanNET and metastatic clear cell RCC. Permanent sections showed nests of clear cells with prominent nucleoli. The neoplastic cells were immunohistochemically positive for neuroendocrine markers synaptophysin, chromogranin and insulinoma- associated protein 1(INSM1), as well as pankeratin and PAX8, with a Ki-67% proliferation index &lt;1%, consistent with low-grade clear cell PanNET. Clear cell RCC marker, CA-IX, as well as adrenocortical marker SF1, were negative.
The combination of immunohistochemical stains is key for making the diagnosis. The previously biopsied conventional PanNET was also identified, which was positive for neuroendocrine markers and had a Ki-67 proliferation index &lt;1%.

Results (if a Case Study enter NA)
NA

Conclusion
Given the rarity of this entity and its strong association with VHL, clear cell PanNET should be considered in the intraoperative consultation to inform clinical management. Furthermore, literature review indicates that metastatic RCC in the pancreas is exceptionally rare in VHL patients and typically of low nuclear grade, suggesting low metastatic potential. Thus, this case emphasizes the diagnostic challenges and the necessity of deferring to permanent sections with immunohistochemical work-up during intraoperative consultation or when assessing small biopsies.
Integrating Whole Slide Imaging and Artificial Intelligence Provides Higher Accuracy in Thyroid Cytology
Authors: Poursina O , Amin A , khayyat A 
Published: October 2024

Abstract

Introduction/Objective
The aim of the study is to evaluate the potential advantages of integrating Whole Slide Imaging (WSI) and Artificial Intelligence (AI) to increase efficiency and diagnostic accuracy in thyroid cytology, especially in indeterminate lesions.

Methods/Case Report
A retrospective database search from 2000-2023 was performed, and the concordance with the pathologists was evaluated based on the manual or AI-based Region of Interest (ROI) identification, the best- suited AI, algorithm design, color enhancement, and combination of AI and Electronic Medical Records (EMR).

Results (if a Case Study enter NA)
The cohort included 3285 WSI and 121,384 ROI. In 109 WSI with manually diagnosed ROI, Deep learning successfully predicted benign and malignant cases, including 11 indeterminate cases, with zero false positives or negatives for 35% of cases. In the second study with 908 WSI, 4494 ROI were identified with Convolutional Neural Network (CNN). A higher area under the curve (AUC) resulted when EMR and Machine Learning algorithm (MLA) were integrated: EMR: 0.931, MLA: 0932, EMR+ MLA; 0.962, Sensitivity: 92.0%, Specificity 90.5%. In the next study with 145 WSI, the CNN-identified ROI was presented to the same pathologist after 117 days. Perfect concordance was seen between the two methods (K score 0.924, time to diagnosis;81.59 Second). In 360 WSI, YOLOV4 algorithm was trained to detect the ROI, and detection and classification rates were used to evaluate the accuracy. It had a precision of 81.84% (3.16% more than the single detection networks of 78.68%). In the last study with 964 WSI, color augmentation improved the AUC for indeterminate cases from 88.3% to 96.2%.

Conclusion
CNN is a better-suited AI for whole slide imaging due to its compatibility with image data and ability to automatically detect important features without human supervision. It also removes the component of subjective bias in interpretation. Color augmentation and integration of EMR can overcome the unique challenges in thyroid indeterminate cytology.
A Case Report of Congenital Wilms’ Tumor and a Comprehensive Literature Review highlighting the spectrum between Wilms’ Tumor and Nephroblastomata’s
Authors: Zhang D , Kakodkar P , Markewich D , Pan H , Hall A , Sinha R , Magee F , Poulin A 
Published: October 2024

Abstract

Introduction/Objective
Wilms’ Tumour (WT) represents the most frequently encountered malignant renal neoplasm within pediatric pathology. To delineate the histopathological features of WT with perilobar nephrogenic rests (PLNR) and intralobar nephrogenic rests (ILNR) from nephroblastomatosis, we report a case with literature review to evaluate the clinical implications of WT with or without nephrogenic rests (NR), and nephroblastomatosis.

Methods/Case Report
Our patient is a 2-week-old neonate with VACTERL, germline mosaic triple X, and stage 1 WT with PLNR and substantial ILNR. The management approach involved radical nephrectomy exclusively. Obtaining a unifying clinical syndrome as well as deciding between WT or nephroblastomatosis was challenging in this case. The molecular testing with VACTERL panel was indeterminate and WT panel revealed DIS3L2 mutation that is indeterminate but likely pathogenic. She has been stable for 12 months and placed on 4-monthly left kidney ultrasound surveillance.

Results (if a Case Study enter NA)
Our literature review showed that the most common histologic subtype in WT patients without NR (n=59) and with NR (n=33) were classic triphasic (28.8%) and stromal-predominant (39.3%), respectively. WT patients with or without NR, underwent radical nephrectomy followed by adjuvant chemotherapy. Loss of heterozygosity (LOH) in TRIM28 was 4-fold higher in cases with NR. Mortality and relapse rates (12.5%) were higher in non-NR cohort. Conversely, nephroblastomatosis patients (n=14) underwent neoadjuvant chemotherapy, ipsilateral radical nephrectomy, and contralateral nephron-sparing surgery. Nephroblastomatosis patients had higher mortality (22.2%) and relapse rate (30%), with no identifiable mutations on molecular testing.

Conclusion
WT patients with NR have an earlier diagnosis and lower mortality and relapse rates compared to those without NR. The higher frequency of LOH in TRIM28 in WT patients with NR warrants future exploration to assess its implication in progression free survival. Nephroblastomatosis exhibits higher mortality and relapse rates, emphasizing the importance of reporting nephroblastomatosis in co-existing WT cases.
Renal Allograft Macrophage Infiltration in Antibody-Mediated Renal Allograft Rejection
Authors: Agrawal V , Kamthan S , Pratap Singh S , Prasad N 
Published: October 2024

Abstract

Introduction/Objective
Macrophages are involved in the pathogenesis and contribute to acute and chronic renal allograft injury. We evaluated CD163+ (M2) macrophage graft tissue infiltration and its correlation with clinical and histological prognostic factors. Urinary soluble CD163, circulating total, and monocyte-derived microparticles (MMPs) in plasma were also estimated and correlated with tissue M2 macrophage infiltration.

Methods/Case Report
The study included forty-five renal allograft recipients with for-cause graft biopsy, with Antibody-mediated Rejection (ABMR) (n=30) or no evidence of rejection (NER) (n=15), from Jan 2021-Dec 2023, along with fifteen age-matched healthy controls (HC). On immunohistochemistry, CD163 positive cells were counted in glomeruli and tubulointerstitium. Urinary sCD163 was done by ELISA. Flow cytometry quantified plasma MPs (AnnexinV+) and MMPs (CD14+/ AnnexinV+).

Results (if a Case Study enter NA)
The mean age of renal allograft recipients was 35±9yrs (all males). Mean s.creatinine in ABMR and NER was 3±2.6 and 2±0.5 mg/dl, respectively. ABMR had significantly more glomerular (16.2±13.7/10 glomeruli) and tubulointerstitial (183±108/10hpf) M2 macrophage (CD163+) cell infiltration than NER (4.8±4.7/10 glomeruli; 133.5±108/10hpf). Urinary sCD163 in ABMR was also significantly raised (0.89±0.63ng/ml) than in NER. It was not detectable in HC. Plasma MMPs were elevated in ABMR [25% of total MPs (1.62x104)] as compared to NER [8.2 % of total MPs (1.4x104)] and HC [7.8% of total MPs (1.2x104)]. In ABMR, the glomerular CD163+ cells correlated with urinary sCD163 levels (r=0.350, p=0.050) and circulating MMPs (r=0.526, p=0.002).

Conclusion
We found that in renal allograft recipients with ABMR, there is significantly higher graft biopsy glomerular CD163+ (M2) macrophage infiltration and elevated urinary sCD163 levels as compared to NER. The plasma circulating MMPs were also elevated in ABMR. Our findings suggest that monocyte activation plays a significant role in the pathogenesis and injury in ABMR. Non-invasive markers of monocyte activation can distinguish ABMR from NER in allograft recipients presenting with allograft dysfunction.
Monoclonal Membranous Glomerulopathy in a Patient with Positive Serology for Lupus Nephritis
Authors: Holmes C J , Li W , Kanaan H D , Zhang P L , Arunselvan S 
Published: October 2024

Abstract

Introduction/Objective
Monoclonal membranous glomerulopathy (M-MGN) is a rare entity; only two reports are available in the literature. Monoclonal membranous glomerulopathy has been called either monoclonal immunoglobulin deposition disease associated with membranous features in a 3-patient small series report or membranous glomerulopathy with light chain restriction in another larger series with 28 cases. We report M-MGN in a patient with positive serology lupus.

Methods/Case Report
The patient was a 74-year-old man with hypertension and nephrotic range proteinuria (protein/creatinine ratio at 8.5). His serum creatinine remained normal at 0.6 mg/dL. The patient was positive for double-stranded DNA and ANA at low titer, but had reduced complement C3 and C4. Immunofixation was negative for monoclonal protein. The light microscopy of the renal biopsy revealed thickened loops of glomeruli with mild interstitial nephritis. Immunofluorescent studies showed a positive linear/granular pattern of IgG and lambda but negative kappa staining along the glomerular loops. Electron microscopy revealed smooth contoured stage 2 subepithelial deposits.
An outside consultation confirmed our diagnosis and found IgG2 restriction in glomeruli. Electrophoresis revealed no monoclonal protein in the serum.

Results (if a Case Study enter NA)
NA

Conclusion
Our patient demonstrated M-MGN with mild interstitial nephritis; the latter may be related to his lupus status. As 30% of patients with M-MGN have either monoclonal serology or B-cell lymphoproliferative disorders, with most having a restricted IgG subtyping, a close follow-up and even chemotherapy for a B-cell clone should be considered.
Mammary Carcinoma Metastasizing to Renal Cell Carcinoma: A Case Report
Authors: Geetha S , Mitchell F , Kashi M , Ort P , Kasturi D 
Published: October 2024

Abstract

Introduction/Objective
The simultaneous occurrence of multiple primary cancers is rare, and even rarer is the phenomenon of one cancer metastasizing to another. Here, we present a case of mammary carcinoma and renal cell carcinoma diagnosed concurrently yet presenting as a cancer-to-cancer metastasis.

Methods/Case Report
A 79-year-old woman, with a 2-week duration of apnea and cough, was found to have right pleural effusion and underwent thoracocentesis. Cytological examination of the fluid revealed malignant cells suggestive of adenocarcinoma. CT abdomen and chest revealed a 1.6 cm right breast nodule, 4.4 cm right axillary mass and right renal lesions measuring 3.0 and 1.6 cm. Core biopsy of the renal lesion showed two populations of cells. One population exhibited moderate cytoplasm and enlarged nuclei displaying anisonucleosis and hyperchromasia arranged singly as well as in sheets and clusters. These cells stained positive for GATA 3, ER, mammaglobin and CK7. Intermixed, were the second population of cells with clear cytoplasm and low nuclear grade forming sheets and replacing renal tissue. These cells were positive for CA9, CD10 and PAX 8 but negative for P40. Based on these findings a diagnosis of low-grade renal carcinoma of clear cell type with a metastatic carcinoma of mammary origin was established.

Results (if a Case Study enter NA)
NA

Conclusion
Renal cell carcinoma and breast carcinoma are known to increase the occurrence of each other. When breast and renal lesions are identified concurrently, the possibility of breast metastasis should be strongly considered. However, the concurrent appearance of renal cell carcinoma harboring metastatic breast cancer is extremely rare.This contributes valuable insights into the complex interplay between different cancer types. Understanding these rare phenomena can aid in refining diagnostic approaches and treatment strategies.
Impact of a PD-L1 Learning Collaborative: outcomes from a mixed-methods evaluation
Authors: Murray S , Lazure P , Kelly M , Beumer K , Kim J 
Published: October 2024

Abstract

Introduction/Objective
PD-L1 Immunohistochemistry testing is often required to determine eligibility for immune checkpoint inhibitor therapy. An ASCP PD-L1 Learning Collaborative (LC) was formed aiming to: 1) identify ways to streamline PD-L1 testing; 2) encourage members to locally implement changes; and 3) develop a resource guide for the community.

Methods/Case Report
The PD-L1 LC (n=38 pathologists and laboratory professionals) participated in 3 activities: 1) 4 meetings in which LC members discussed current literature and practice; 2) 3 30-minute on-demand, credit-bearing panel videos, in which selected LC members summarized the LC outputs and shared their experiences; and 3) a guide summarizing resources relevant to streamlining PD-L1 testing. The mixed-methods evaluation included: 1) five- minute surveys before (n=24), immediately after (n=11) and 7-months post-LC (n=17); 2) polling questions (2-4 per meeting); 3) semi-structured interviews (n=5). Quantitative data was analysed using descriptive and inferential analysis, qualitative data using a thematic analysis / inductive reasoning approach.

Results (if a Case Study enter NA)
Baseline data confirmed delays in testing caused by unstandardized PD-L1 testing processes and suboptimal confidence in PD-L1 validation and methodologies. Post-LC, members self-reported perceived increased knowledge and higher confidence levels regarding discussion of PD-L1 scientific evidence and best practices. At the 7-month follow-up, 59% of respondents reported at least one PD-L1-related practice change, with 29% of participants selecting:1) Improving protocols for specimen acquisition, handling, or processing; 2) Improving communication with multidisciplinary care team; 3) Optimizing biomarker testing workflows. Remaining suboptimal knowledge post-LC suggests need for further educational efforts. Participants identified “Tumor-specific considerations” as the main resource missing for PD-L1 testing.

Conclusion
A learning collaborative has shown impact in improving PD-L1 testing processes and related practices among a group of pathology professionals. The group successfully made available three panel videos and a resource guide, and PD-L1-related practice changes were reported. Future initiatives should address remaining gaps and develop tumor-specific PD-L1 testing considerations.
Illustration of the Financial Impact of Usage of Initial Specimen Diversion Devices (ISDD) or Continued Educational Initiatives on the Costs from Blood Culture Contamination
Authors: Petersen J M , Jhala A 
Published: October 2024

Abstract

Introduction/Objective
Blood culture contamination (BCC) has the potential to lead to additional healthcare system costs and harm to patient. Two ways to reduce BCC have been explored in the literature and are economically modeled including initial specimen diversion devices (ISDD) and continued education on phlebotomy.

Methods/Case Report
A literature review on the economic costs of BCC, ISDD efficacy, and phlebotomy education to reduce BCC rates was undertaken. The reported average BCC at a veteran affairs medical center (VAMC), its reported rate during a month of phlebotomy training, the cost of an ISDD device at VAMC, and the average wage for 4 hours of phlebotomy manager time for training was noted. An illustrative economic model involving 100 patients was used at BCC rates of 1%, 2%, and 3% along with what had been observed at the VAMC was used for economic modeling.

Results (if a Case Study enter NA)
It was previously reported by Skoglund et al that in laboratories with rapid diagnostic testing modalities (such as MALDI-TOF or PCR testing), the cost per BCC event is $13,026 versus $8,287 in costs for a negative blood culture. ISDD efficacy in the literature reviewed (74.1% to 87.5%), continuous education efficacy (16.2% to 57.8%), ISDD device cost ($17.70 per device), and the hourly wage of a phlebotomy supervisor ($29.34) were noted. The reported average BCC rate from a regional VAMC was 1.33%, and during the month with education, the rate was 0.5%. From a model of 100 patients, ISDD device savings ranged from $1,741.60-$2,376.63 (1% BCR), $5,253.20-$6,523.25 (2% BCR), and $8,764.79-$10,669.88 (3% BCR). Education savings ranged from $755.98-$2,727.41 (1% BCR), $1,523.70-5,466.55 (2% BCR), and $2,291.42-$8,205.69 (3% BCR). The observed impact of education at the regional VAMC would have resulted in savings of $650.83 per 100 patients.

Conclusion
Both education and ISDD devices can result in significant savings from the costs of BCC.
Evaluation of Anti-k Antibody in a Patient Undergoing Redo Sternotomy
Authors: Abdelmonem M , Ngo N , Cabungan M , Papakonstantino K , Jurado C , Osterlund A , Cai W , Virk M S , Yunce M 
Published: October 2024

Abstract

Introduction/Objective
Introduction: The Kell blood group system, discovered in 1946, holds paramount significance in transfusion medicine and hemolytic disease of the newborn (HDN). Named after Mrs. Kelleher, who exhibited anti-Kell antibodies resulting in HDN, this system comprises 25 antigens, with the original K antigen retaining primary importance. Additionally, Levine et al. identified anti-Cellano, now known as anti-k, presenting an antibody antithetical to anti-K.

Methods/Case Report
Case Presentation: A 60-year-old male with a history of bioprosthetic aortic valve insufficiency, pulmonary homograft stenosis, and recurrent aortic insufficiency presents for a fourth redo sternotomy for root and ascending aorta replacement. Preoperative assessment revealed a positive antibody screen for anti-k, a clinically significant antibody associated with decreased survival of transfused red blood cells (RBCs). Given limited compatible blood units available, efforts are underway to secure additional donations before the scheduled surgery on 2/22/24.
The patient’s medical history indicates no recent blood transfusions or iron therapy, with the last transfusion in 1996. He is anticoagulated with warfarin for mechanical valve and atrial fibrillation, necessitating preoperative bridging with Lovenox injections.

Methods
The patient’s antibody screen and initial panel demonstrated pan-reactivity with 3+ reactivity, suggesting an antibody targeting a high-frequency antigen. Further testing using polyethylene glycol (PEG) confirmed the presence of anti-k, supported by negative reactions to additional K-negative cells. The absence of other clinically significant antibodies was verified using 0.2 M Dithiothreitol (DTT) modified cells.

Results (if a Case Study enter NA)
NA

Conclusion
Conclusion: The identification of anti-k antibody underscores the critical role of preoperative antibody screening in mitigating transfusion-related complications, particularly in patients requiring complex surgical interventions. Collaborative efforts between clinical teams and transfusion medicine specialists are imperative to ensure adequate blood product availability and optimize patient outcomes.To prevent further exposure, it is recommended that patients with rare antibodies carry an Antibody ID card indicating the rare antibody they possess.k antigen blood donors are underrepresented in the general donor pool. It is recommended to develop a systematic recruitment for k antigen donors.