bluuebunny/crossref_metadata_2025 huggingface dataset:
Solitary Loss of PMS2 in a patient with Colon carcinoma
Authors: Umah C , Singh N
Published: October 2024

Introduction/Objective

In the United States, there are about 150,000 new cases of Colorectal cancer (CRC) and about 50,000 CRC related deaths each year. Hereditary nonpolyposis colorectal cancer (Lynch Syndrome) accounts for 2% - 4% of CRC. It is characterized by germline mutations in mismatch repair (MMR) genes - MLH1, MSH2, MSH6 and PMS2. Patients with Lynch syndrome have up to an 80% lifetime risk (LTR) of CRC and up to 60% LTR of endometrial cancer. Lynch syndrome patients also have an associated LTR of ovarian cancer (38%), upper urologic tract cancer (18%), gastric cancer (13%), small bowel cancer (6%), hepatobiliary tract cancer (4%), and brain tumors (3% - usually glioblastoma).

Methods/Case Report

A 76-year-old man with history of moderately differentiated colorectal adenosarcoma involving the transverse colon and a recently diagnosed grade group 5 (Gleason 4 + 5) prostate adenocarcinoma, currently being managed at an outside hospital. The case was sent to UAB for DNA MMR/microsatellite instability (MSI) status evaluation testing. Immunostaining showed loss of PMS2 and intact expression of MLH1, MSH2 and MSH6. These results were confirmed by the IdyIIa MSI assay which detected microsatellite instability in 5 of 7 markers and negative for BRAF V600E variant confirming microsatellite instable tumor.

Results (if a Case Study enter NA)

NA

Conclusion

Solitary loss of PMS2 in colonic adenocarcinoma is uncommon and may be caused by an underlying germline mutation of MLH-1 or PMS2, thus could represent Lynch Syndrome. Our patient’s age doesn’t favor Lynch syndrome. Next step would be to perform MLH-1 promoter methylation to confirm sporadic nature of carcinoma.

Somatic methylation of the MLH1 promoter occurs in approximately 80% of CRC with defective MMR. Prostate cancer is not currently considered a part of Lynch syndrome.
DNA Methylation Profiling Confirms a Challenging Glioblastoma, Atypical Mesenchymal Type Which Mimics Intracranial Mesenchymal Tumor
Authors: Aljumaili Z , Ibrahim N , Gao Y , Rivera D , Bhattacharjee M , TAKEI H , Zhang X
Published: October 2024

Introduction/Objective

Brain tumors exhibit distinct DNA methylation patterns that reflect their cellular origin, molecular subtype, and clinical behavior. DNA methylation signatures provide valuable insights into tumor heterogeneity, evolution, and treatment response, guiding personalized therapeutic strategies. Our case, glioblastoma, atypical mesenchymal type confirmed by DNA methylation profile and it reflects the clonal evolution of the glioblastoma metaplasia with minimal glial component which was histologically challenging.

Methods/Case Report

A 56-year-old gentleman presented with headaches. MRI brain demonstrated a heterogeneous enhancing mass with areas of central necrosis in the left temporal lobe, measuring approximately 49 x 34 mm, with surrounding T2 FLAIR hyperintensity extending into the left basal ganglia, causing compression of the left lateral ventricle and uncal herniation. He underwent left-sided craniotomy for tumor resection. Microscopic examination revealed hypercellular spindle cell neoplasm, forming fascicles. Brisk mitotic activity and geographic necrosis were evident. GFAP highlighted narrow margins of the tumor which could represent the entrapped glial tissue. CD99 stained the tumor cells, Other immunohistochemical stains for spindle cell work up, like S100, EMA, PR STAT6 and desmin were all negative. A diagnosis of intracranial mesenchymal tumor /sarcoma was considered.

Methylation profiling results showed class calibrated scores of 0.9741, compatible with Glioblastoma, IDH-wildtype, atypical mesenchymal type with a cytogenetic profile including gain of chromosome 7 (including EGFR) and loss of chromosome 10 (including PTEN), and loss of CDKN2A/B.

Results (if a Case Study enter NA)

NA

Conclusion

Although histopathological examination and immunohistochemical study are fundamental in diagnosing brain tumors, the rapid development of cytogenetic and molecular diagnostic modalities has significantly contributed to diagnostic accuracy and the potential for targeted treatment. Particularly, DNA methylation profiling has proven valuable in diagnosing morphologically challenging cases with prognostic value. Eventually, DNA methylation profiling will be adopted as a major cancer diagnostic criterion and will become a standard procedure performed at major academic centers.
Bihemispheric IDH-Wildtype Glioblastoma with Unilateral FGFR3-TACC3 Fusion in Patient with Breast Cancer History: A Case Report and Literature Review
Authors: Farooq S , Zeches B A , Boyer P , Lee S , Jo J
Published: October 2024

Introduction/Objective

Adult IDH-wild type glioblastomas comprise a heterogeneous spectrum of neoplasms, characterized by poor prognosis and resistance to the chemoradiotherapy. For WHO integrated diagnosis classification and to establish treatment options, molecular analysis is necessary. Herein, we present a case of a glioblastoma, IDH-wildtype with involvement of both cerebral hemispheres and an uncharacteristic in-frame fusion limited to one hemisphere.

Methods/Case Report

The patient is a 52-year-old woman with past medical history of metastatic breast cancer who presented with headache and worsening facial pain. Brain magnetic resonance imaging brain demonstrated a right frontal lobe lesion with vasogenic edema. The patient was treated with Gamma Knife radiosurgery. Scans revealed enlargement and a new left frontal lobe lesion. Bihemispheric tumor resection and GammaTile placement was undertaken.

Results (if a Case Study enter NA)

Histologically, the tumor was composed of hypercellular astrocytes, microvascular proliferation, and necrosis with no evidence of metastatic disease. Immunohistochemistically, neoplastic cells showed glial fibrillary acidic protein expression and elevated Ki-67 proliferation index. Molecular examination revealed in the right hemisphere lesion post-radiation (1) FGFR3::TACC3 (exon 17::exon 11) fusion and (2) TERT promoter, while the left hemisphere lesion which did not receive radiation showed clinically relevant variants in (1) TERT promoter, (2) TP53, (3) NF1, and (3) PIK3CA without identification of a fusion. An integrated diagnosis of glioblastoma, IDH- wildtype, CNS WHO grade 4 was established bilaterally.

Conclusion

The fibroblast growth factor receptor 3 (FGFR3)-transforming acidic coiled-coil 3 (TACC3) fusion is identified as a rare molecular feature in glioblastomas with an estimated prevalence of 4%. Clinical trials suggest that F3T3-positive tumors have a better prognosis than those without the translocation. The identification of the oncogenic FGFR3-TACC3 fusion highlights the possibility of identifying patients potentially responsive to targeted therapy with FGFR kinase inhibitors. The significance of the molecular differences in the right and left hemisphere lesions is uncertain; glioblastomas are heterogeneous tumors with intra-and intertumoral heterogeneity but it may suggest independent origins.
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

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

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 <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 <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

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

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

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

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

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

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

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

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.
Anti-LAN Antibodies: Clinical Implications and Case Presentation
Authors: Abdelmonem M , Ngo N , Cabungan M , Virk M S , Cai W , Shan H , Chang S , Yunce M
Published: October 2024

Introduction/Objective

The LAN system, originating from the 901 Series of High Incidence antigens, transitioned to a recognized System in 2012. The LAN antigen, situated on ABCB6, a multipass membrane protein associated with porphyrin transport, plays a crucial role in heme synthesis. Functionally, LAN acts as an ATP-binding cassette transporter on the red blood cell membrane. Comprising a single antigen, LAN exhibits elevated expression in various tissues including the heart, skeletal muscles, fetal liver, mitochondrial membrane, eye, and Golgi apparatus. Notably, LAN shows no specific association with any particular geographic or ethnic group. Resistant to Ficin/Papain, Trypsin, α-Chymotrypsin, and 0.2M DTT, LAN antibodies primarily consist of IgG and necessitate IAT for detection. While Anti-LAN has been implicated in Hemolytic Transfusion Reactions (HTRs), its involvement in Hemolytic Disease of the Fetus and Newborn (HDFN) remains infrequent. LAN-negative blood is exceedingly rare, often requiring Monocyte Monolayer Assay Testing (MMA) for clinical assessment.

Methods/Case Report

Case Presentation: An 81-year-old female with a medical history including seizure disorder, hypertension (HTN), hyperlipidemia (HLD), gastroesophageal reflux disease (GERD), small bowel obstruction, and high-grade de-differentiated metastatic retroperitoneal liposarcoma presented for preoperative evaluation. A type and screen ordered as part of outpatient preoperative assessments revealed a positive antibody screen. Further investigation traced the origin of the anti-LAN antibody to an external facility since 2017. Antibody identification indicated the reactivity of the patient’s plasma with all cells (1+ AHG in PEG), excluding the auto control. Utilizing rare frozen antisera anti-LAN, the patient was phenotyped for LAN, yielding a LAN-negative status. Subsequent testing with three rare frozen LAN-negative group O cells aimed to exclude clinically significant antibodies. Differential adsorption, employing a comprehensive baseline RBC phenotype record obtained from the external facility, ruled out anti-E, anti-K, and anti-Fyb, thereby confirming Anti-LAN specificity.

Results (if a Case Study enter NA)

NA

Conclusion

The exceptional rarity of LAN-negative blood underscores the high prevalence of reactivity to Anti-LAN antibodies, exceeding 99% in most populations. In select cases, autologous transfusion may emerge as a viable management strategy. Consequently, the patient’s surgical procedure has been deferred, with no immediate requirement for blood products.
A 6-month Review of pRBC Transfusion Practices in a Tertiary Institution in Brooklyn, NY
Authors: Haque A , Agaronov M , NGICHABE J , Gabutan E , Talabong D , Rana-Gupta T , Yakut E , Kang S
Published: October 2024

Introduction/Objective

Many factors are considered when managing hospital blood inventory. Because demographics and types of services vary per institution, a conscious effort to survey the prevalence of different blood types is necessary to make better predictions of inventory adequacy and decrease inappropriate use of O pRBC units.

Methods/Case Report

We reviewed the transfused pRBC units between October 2023 and March 2024 to determine the number of patients receiving ABO-type specific units and the number of D+ patients receiving D- units.

Results (if a Case Study enter NA)

After review, the patient population was found to be approximately 80% African Americans. Most of our patients were D+ with a monthly average of 224 patients. In contrast, we served 15 D- patients per month (PPM). Between 21-33% of D+ patients received D- units. O blood type was the most common, with an average of 224 PPM, followed by A blood type at 57 PPM and B blood type at 51 PPM. Since we see an average of 10 AB blood type patients monthly, it wasn’t surprising that they all received non-type specific units. Noteworthy is the significant proportion of A and B blood type patients receiving ABO type-specific units, ranging from 74-85% for A blood type and 70-90% for B blood type.

Conclusion

Our institution’s commitment to hemovigilance and conservation of O units is evident in the relatively high percentage of patients receiving ABO-type specific units. It is worth noting that we are a tertiary institution mainly serving the African American population. This creates a unique need to maintain adequate O units for emergency transfusion and increase the possibility of using O units to meet our sickle cell disease patients’ needs. Given that our demographics are primarily D+, some of our D- units were utilized in D+ patients. By adhering to our transfusion protocol and surveying our patients’ ABO and D blood types, we can anticipate our inventory needs and help prevent future O pRBC shortages.
Removal of Isolated Cannabis Use as an Order Indication for Urine Drug Screening (UDS) Eliminates Racial Inequity in Maternal UDS Testing and Reporting to Child Protective Services
Authors: Azimi Vahid , Trammel Cassandra , Zaydman Mark , Jackups Ron , Kelly Jeannie
Published: October 2024

Black patients on labor and delivery (L&D) units are more likely to undergo urine drug screening (UDS) and subsequent mandated reporting to child protective services (CPS), which can result in increased separation of the parent and infant, contributes to systemic inequities, and erodes the patient/provider relationship. These disparities are driven by a testing indication of isolated cannabis use (ICU), which based on previous data from our institution, disproportionately selects Black patients for testing. In October 2022, the Barnes-Jewish Hospital (St. Louis, MO) L&D unit removed ICU as a UDS indication; concurrently, we implemented an electronic health record (EHR)-based order question requiring providers to select an indication for testing. The objective of this study was to analyze the impact of this intervention on racial equity in UDS testing and CPS reporting. Data on deliveries, UDS testing, and CPS reports were obtained from the EHR, and data for deliveries occurring during the pre- (1/1/2020-9/30/2022; 33 months) vs. post-implementation (10/1/2022-2/1/2024; 16 months) periods was compared. There were a total of 9,187 and 4,757 deliveries during the pre- and post-implementation periods, respectively. At baseline, there were more deliveries by Black patients in the pre-implementation (47.8%) vs. post-implementation (44.0%) period (p<0.001); there was no difference in age, multiparity, or neonatal outcomes between the two periods. In the pre-intervention period, 29.2% of Black and 13.8% of White patients had UDS testing (p<0.001), and 7.6% of Black and 4.1% of White patients underwent reporting to CPS (p<0.001); in the post-intervention period, 4.5% of Black and 3.6% of White patients had UDS testing (p=0.52), and 4.2% of Black and 3.5% of White patients underwent reporting to CPS (p=0.52). 34.6% vs. 67.8% of UDSs in the pre- and post-implementation were positive for any non-cannabis compound, respectively (p<0.001). In conclusion, removing ICU as an order indication dramatically improves racial equity in UDS testing and CPS reporting on a L&D floor, and improves the pre-test probability of UDS testing for non-cannabis compounds.
Value of Functional Protein S Activity Assays for Detection of Type II Protein S Deficiency
Authors: Marsden Katharine , Gil Morayma Reyes , Bauman Shelbey , Tomsich Cleveland Clinic Robert J , Tomsich Robert J
Published: October 2024

Background

Protein S deficiency is a hereditary thrombophilia which occurs in three forms: Type I (quantitative), type II (qualitative) and type III (qualitative due to a gain of function). Literature suggests that of these, type II is the rarest and most difficult to diagnose. Type II protein S deficiency is only detectable by assaying protein S activity with a functional, clot-based test. However, this test is susceptible to interference and has a lower specificity when compared to antigen assays used to detect free and total protein S levels. Subsequently, the Choosing Wisely Guidelines released by the ABIM Foundation recommends against using protein S activity assays entirely. Instead, they suggest using only free protein S antigen assays. Although the rationale is to avoid false positive results from the protein S activity assay, it ultimately may result in a failure to detect type II protein S deficiency.

Objective

This study, performed at a tertiary medical center in the Midwestern region of the United States, aims to determine the proportion of false positives in functional assays as well as the percent of true type II protein S deficiency cases within this testing population.

Methods

All cases with abnormal protein S function within the institution were evaluated from July 2018 through July 2023 and classified as acquired or hereditary deficiencies. Cases were classified as acquired if there was evidence of liver disease, vitamin K deficiency, ongoing thrombosis, consumption, disseminated intravascular coagulopathy, or pregnancy. Possible hereditary deficiency cases were classified as type I, type II and type III: Type I if all assays were low, type III if both active and free protein S assays were low with normal total protein S, and type II if only protein S activity was low. The cutoff defined for normal total and free protein S levels was greater than 70% activity, and the low protein S activity cutoff was defined as less than 50%. Patients with low protein S activity but normal immunologic protein S and an elevated factor VIII were considered falsely low values. Chart review will be performed for remaining cases with low protein S activity to rule out confounders such as vitamin K deficiency, warfarin use, acute phase reaction, or pregnancy.

Results

From a total of 8805 panels performed to assess for possible thrombophilia, 1580 (18%) were found to have decreased protein S activity. Of these cases, 599 (38%) were considered falsely decreased due to elevated factor VIII levels. 322 cases (3.7%) were considered possible hereditary deficiencies: 217 type III (2.5%), 27 type II (0.3%), and 80 type I (0.9%).

Discussion

Our data indicates the prevalence of subtypes may be differently distributed than previously believed, which may call for current guidelines to be reevaluated.
Cherry-Red Plasma Unraveling the Impact of PV-10 on Chemistry Assays
Authors: Chen Lechuang , Zhang Yu , Meng Qing H
Published: October 2024

Background

The accuracy of clinical laboratory measurements can be compromised by laboratory test interferences. PV-10 (Rose Bengal), a chemotherapy medication used in the treatment of metastatic melanoma, was observed to cause a cherry-red discoloration in plasma. This plasma color change, resembling hemolysis, raises serious concerns about potential interference in clinical laboratory tests. Our study focused on understanding the potential interference of PV-10, particularly the impact on the hemolysis index (H index) and various chemistry assays to ensure result accuracy in cancer treatment.

Methods

To investigate the potential interference of PV-10, pooled normal and high baseline bilirubin plasma samples were spiked with a gradient of PV-10 concentrations (0 to 22 µg/100µL). Samples were analyzed on Roche Cobas 8000 analyzer with H index and all the chemistry assays measured.

Results

The presence of PV-10 in plasma significantly increased the H index, in a dose-dependent manner. Specifically, the H index increased from 14 (control plasma) to 2643 at the highest PV-10 concentration (22 µg/100µL) in pooled plasma. Among all chemistry assays, most of them were not affected by PV-10. However, certain assays like IRON have dose dependent increase with PV-10 concentration. CHO2A (Total Cholesterol), TP (Total Protein), and TRIG (Triglycerides) have shown a consistent increase trend. In contrast, the DBILI values decreased with increasing PV-10 concentrations, from 6.7 mg/dL to 0.2 mg/dL. TBIL levels also demonstrated a gradual decline from 9.6 mg/dL to 8.4 mg/dL as PV-10 concentration increased in pooled high baseline bilirubin plasma.

Conclusion

This study provides insights into the potential interference of PV-10 in clinical chemistry assays. The elevated H index by PV-10 is not attributed to hemolysis. It is imperative for both laboratory professionals and care providers to recognize the implications of PV-10-induced plasma discoloration and its potential interference in laboratory tests.
Using Laboratory Documentation to Extend a Large Language Model to Serve as a Laboratory Assistant
Authors: Shean Ryan , Ng David
Published: October 2024

Demographic and structural changes in the workforce are resulting in ever smaller cohorts of laboratory medical professionals while medical advancements and an aging population has increased demand for laboratory testing. Furthermore, the inexorable aging of our technologists has resulted in a workforce with a high variation in experience. The need for new tools to help bridge the experience gap and increase productivity are readily apparent. Recently, large language models (LLMs) have emerged as powerful tools in various industries, including healthcare. However, numerous concerns have been raised regarding data security particularly with respect to proprietary and patient data. Furthermore, these models must be adapted to function effectively within the unique context of laboratories. To this end, we present a proof of concept project that uses laboratory documentation to extend a locally run LLM to serve as a laboratory assistant.

To develop this tool, we collected and analyzed job aids, SOPs, multidisciplinary guidelines, and classification systems relevant to a particular laboratory at our institution. We then used retrieval augmented generation (RAG) on these documents to locally extend open source large language models to understand laboratory-specific terminology, procedures, and contexts.

Preliminary results suggest that the language model can accurately process and generate responses related to specific lab tasks, including sample handling, testing protocols, and data interpretation. For example, it can suggest possible differential diagnoses based on test results and generate suggested follow-up tests even for complex workflows such as leukemia/lymphoma flow cytometry.

By using existing specific laboratory documentation as training data, we have demonstrated that it is possible to securely adapt large language models to function effectively within the context of laboratories. This represents an essential step towards integrating advanced technologies into the laboratory. Future work includes evaluating the language model’s performance in different lab settings and expanding its functionality. We envision that this project could evolve into an integral component of laboratories’ digital infrastructure, hopefully enhancing training, knowledge sharing, and operational efficiency.
Enhancing Early Detection of Prostate Cancer Using PSA-Guided Screening in High-Risk Men Under 50
Authors: Chen Lechuang , Meng Qing H
Published: October 2024

Background

Prostate Cancer remains a significant global public health concern. It is the most common cancer and the second leading cause of cancer death among men in the United States. Current guidelines, including those by the USPSTF, ACS and ASCO offer varying recommendations on PSA screening. Present clinical practice, primarily targeting men aged 50-69. Our study aimed to assess the feasibility and validity of using PSA for targeted screening in men under 50 who are at high risk, enhancing early detection of prostate cancer.

Methods

This retrospective analysis utilized data from our hospital’s prostate cancer screening program collected from 2022 to 2023, including104 individuals under 50. Participants were categorized based on PSA levels 4-10 ng/mL (n=71) and over10 ng/mL (n=33). We analyzed the number of cases diagnosed with prostate cancer and the correlation with PSA levels, Gleason Scores (GS), family history, and ethnicity/race.

Results

In the104 participants, 88 of them were diagnosed with prostate cancer, highlighting an 84.6% detection rate. Among PSA levels 4-10 ng/mL group, 36 out of 43 White or Caucasian and 13 out of 13 Black or African American men were identified as GS 6-10. In the group PSA over 10 ng/mL, 18 White or Caucasian and 6 Black or African American individuals with more aggressive disease (GS 6-10). Importantly, a substantial fraction of these cases had a first-degree relative with prostate cancer, emphasizing the influence of family history on PSA screening decision.

Conclusion

Our findings suggest that PSA-guided screening in men under 50 at high risk can enhance the early detection of prostate cancer. The significant presence of intermediate-risk prostate cancer (GS 6 or 7) in populations at higher risk due to ethnicity/race and family history. Our study highlights the potential benefits of revisiting current screening guidelines to lower the age threshold for high-risk populations.