bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical Presentation in Sclerosing Epithelioid Fibrosarcoma: A Case Report
Authors: Miller L J , Saterbak A , Parsons L N , Singh R , Bone K M 
Published: November 2022

Abstract

Introduction/Objective
Sclerosing Epithelioid Fibrosarcoma (SEF) is a rare sarcoma with characteristic EWSR1::CREB3L1 fusion and MUC4 positivity by immunohistochemistry (IHC). SEF most often presents as a primary soft tissue tumor in the lower extremities. Histologically, SEF is characterized by cords, nests or sheets of monotonous, epithelioid tumor cells in a dense collagenous background. We report a case of SEF in an atypical location with unique histological and atypical cytogenetic findings.

Methods/Case Report
A 13-year-old male presented with left leg and back pain. A CT scan demonstrated a 7.3 x 5.7 x 6.8 cm left hemiabdomen mesenteric mass with metastatic nodules in the pancreas, liver, L1 vertebrae and sacrum. Sacral biopsy demonstrated infiltrative and discohesive nests of small to medium round cells with scant eosinophilic to clear cytoplasm but without conspicuous tumor stroma. An extensive IHC panel was positive only for CD99. Fluorescence in-situ hybridization (FISH) demonstrated an unusual finding with a variant pattern. FISH revealed an EWSR1 rearrangement with an unidentified partner. The tumor karyotype was normal in the dividing cells utilized for chromosome analysis, suggesting the rearrangement was enriched in the non-dividing cell population. Next- generation sequencing (NGS) revealed a EWSR1::CREB3L1 fusion that was confirmed by FISH, and MUC4 was positive by IHC, further supporting classification as SEF.

Results (if a Case Study enter NA)
NA

Conclusion
Due to the atypical presentation and histologic appearance of this rare sarcoma, integration of IHC, FISH, and NGS were required to fully characterize the lesion.
A Challenging Case of Atypical Papillary Proliferation of Nipple with Loss of Myoepithelial Layer Cells; a Diagnostic Dilemma
Authors: Pettit K , Rahmanov N , Hassan M 
Published: November 2022

Abstract

Introduction/Objective
Papillary breast lesions are comprised of a broad spectrum of entities ranging from benign conditions like intraductal papilloma to invasive carcinoma. These lesions account for less than 3% percent of breast tumors and less than 2% of breast malignancies. The wide range and overlap in the clinical, imaging, and histologic characteristics of these lesions can often make them difficult to classify. Here we present a case of a challenging neoplastic nipple papillary lesion with a differential diagnosis ranging from nipple adenoma with atypia to papillary carcinoma.

Methods/Case Report
48-year-old female with history of left nipple mass for 6 months, presented to the emergency department with mild bleeding from the left nipple for two hours. Breast ultrasound showed a group of fine pleomorphic calcifications within a mass arising from the left nipple, highly concerning for Paget's disease. Histopathology revealed papillary proliferation of well-formed round structures within a variably fibrous/hemorrhagic stroma. The nodules exhibited papillary fronds with epithelial hyperplasia of monotonous low-grade cells, and scattered mitoses, forming relatively rigid/luminal structures with polarization. No desmoplasia or conventional infiltrative pattern was seen. Immunohistochemical staining showed strong expression for estrogen receptor (ER). Cytokeratin 5/6, p63 and calponin did not highlight the myoepithelial layer in the papillary elements or around the round structures. A diagnosis of atypical papillary proliferation was rendered to warrant an excision. Subsequently, the patient underwent total mastectomy, which revealed conventional invasive ductal carcinoma with lymphovascular space invasion.

Results (if a Case Study enter NA)
NA

Conclusion
Atypical papillary lesions of the nipple are difficult to classify in a limited biopsy material. The loss of myoepithelial cell layer makes interpretation even more challenging. Extreme caution should be taken in assigning neoplastic nature to the lesions in biopsy which eventually guide the surgeon in making decision to preserve the nipple or not.
Education to Improve Ki67 Testing in Hormone Receptor-Positive/HER2-Negative Early-Stage Breast Cancer (HR+ EBC)
Authors: Kelly M , Obajimi O , Rosenthal K M , Quill T , Beumer K 
Published: November 2022

Abstract

Introduction/Objective
Ki67 is a marker of active cellular proliferation with prognostic utility in EBC. However, clinical use has been limited due to variability in assay protocols and interpretation. Recently, a Ki67 companion diagnostic received FDA approval for assessing recurrence risk and guiding therapy decision-making for high-risk HR+ EBC. We report a comprehensive program to understand current clinical use of Ki67 and identify and address educational needs of healthcare professionals regarding Ki67 testing to improve patient care.

Methods/Case Report
The multimodal program included a baseline survey to explore gaps in knowledge, skills, and clinical confidence in Ki67 assessment; a live, virtual webinar featuring a pathologist and an oncologist discussing practice-changing developments; and an interactive on-demand webcast developed from the webinar.

Results (if a Case Study enter NA)
Of the 653 survey respondents (227 self-identified a role in medical oncology and 261 in pathology), 77% indicated that they currently test for Ki67 in patients with HR+ EBC, and 64% indicated they were very or moderately knowledgeable on how to use Ki67 as a diagnostic assay. However, only 46% indicated they were very or moderately knowledgeable about the strengths and limitations of Ki67 testing methods or identifying patients who would likely benefit from CDK4/6 inhibition. At the end of the webinar, 67% to 83% of the evaluation respondents (92 – 115) indicated that the education increased their knowledge and/or confidence around how to use and test for Ki67 and identify eligible patients. There were also statistically significant gains from the webcast, including knowledge of strengths/limitations of Ki67 testing methods and confidence in the ability to identify patients for targeted therapies or clinical trials.

Conclusion
These data suggest some challenges in integrating Ki67 as a biomarker for clinical practice, but education can enhance knowledge and confidence on this topic. A detailed analysis of the survey and outcomes from the linked education are presented.
Pembrolizumab-Induced Sarcoid-Like Reaction of the Breast
Authors: Ibarro A , Vial C , Torres S , Itriago L 
Published: November 2022

Abstract

Introduction/Objective
Immunotherapy provides an efficacious and durable therapeutic option for patients with advanced-stage neoplastic disease. Related adverse events are several. Sarcoid-like granulomatous reaction is a rare, not severe complication, more frequent in skin, lung and lymph nodes. It should not be misdiagnosed as tumor recurrence or progression.

Methods/Case Report
Case Report.

Results (if a Case Study enter NA)
Female 50 years old. Smoker for 40 years until 2016. Reumathoid arthritis at age 50. Palmo-plantar psoriasiform dermatitis since 2016. Sporadic corticoids use and topic therapy. Lung adenocarcinoma in june 2021, multifocal, acinar-papillary, pT4-pN1- pM1a. TPS PD-L1 70%. In treatment with pembrolizumab since july 2021, without toxicities. In november 2021, after 6 doses, PET/CT shows mild growth of bilateral nodules. Stereotaxic breast biopsy for microcalcifications of recent appereance in january 2022. Pathology report: “Sarcoid-like reaction. Microcalcifications, present in biopsied material, not visualized after cuts of all tissue (mecanically displaced). PAS, Grocott and Ziehl-Neelsen negatives”. Currently, after 16 cycles of pembrolizumab, the patient is in good condition.

Conclusion
Sarcoid-like reaction (epithelioid non necrotizing granulomas), during immunotherapy is rare, can be seen especially in skin, lung, mediastinal lymph nodes. For some authors it would be a marker for therapy response and correlated with improve overall survival. It is very important to differentiate this reaction with progression or recurrence of tumor disease. Our case is the first immunotherapy induced sarcoid-like reaction described in the mammary gland.
Case Report: Primary Alveolar Soft Part Sarcoma of the Breast
Authors: Abdelmalak M , Jeck W , Bentley R C , Factor R E , Rosenberger L H , Peterson D E 
Published: November 2022

Abstract

Introduction/Objective
Alveolar soft part sarcoma (ASPS) is an exceedingly rare malignant neoplasm, typically arising in the lower limbs or the head and neck region of children and young adults. Very few cases of primary ASPS have been reported arising in the breast.

Methods/Case Report
A 16-year-old female presented with a slowly growing mass of the left breast for three years. Clinical and imaging features were initially consistent with a fibroadenoma. Palpable increase in size prompted repeat ultrasound revealing a 3.4 cm oval, complex, cystic and solid mass. Due to its complexity by imaging and interval growth, biopsy was recommended. The biopsy demonstrated a cellular, vascular, and nested tumor consisting of polygonal cells with abundant granular eosinophilic cytoplasm and round nuclei with prominent nucleoli. Tumor cell discohesion and pseudoalveolar growth pattern were also seen in several areas, while necrosis and increased mitoses were not identified. The histologic findings were not consistent with a fibroepithelial lesion. The differential diagnosis included apocrine adenosis, granular cell tumor, melanoma, acinic cell carcinoma and ASPS. By immunohistochemistry, the lesion demonstrated strong and diffuse positivity for TFE3, MyoD1 and desmin. It was negative for pancytokeratin, CD68, S-100, HMB45 and smooth muscle actin. A TFE3 gene rearrangement was detected by FISH. The morphologic, immunohistochemical, and molecular findings were most consistent with ASPS. At resection, the tumor was entirely confined to the breast, with no involvement of the chest wall. No other potential primary sites were found by imaging work-up.

Results (if a Case Study enter NA)
NA

Conclusion
Although ASPS has distinctive histologic and molecular features, it may cause diagnostic dilemmas when arising in unusual sites. Here we report a highly unusual case of a primary ASPS arising in the breast of a teenager, which clinically mimicked a fibroadenoma. While this is a rare entity, it supports the biopsy of any breast mass with interval growth.
Engaging Pathologists in a Peer-to-Peer Learning Collaborative on HER2-Low Breast Cancer
Authors: Kim J , Kelly M , Beumer K 
Published: November 2022

Abstract

Introduction/Objective
Recent advances in research have shown clinical effectiveness when targeting the lower range of HER2 expression (ie, HER2-low) in patients with metastatic breast cancer. American Society for Clinical Pathology worked in collaboration with Q Synthesis to develop a peer-to-peer learning collaborative to proactively prepare pathologists for HER2-low. This CME project was supported by an educational grant from AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc.

Methods/Case Report
38 pathologists participated in the ASCP HER2 Breast Trailblazers. For foundational knowledge, learners completed online modules covering scientific updates on HER2-low. Through small-group, case- based discussions, learners reviewed operational challenges and opportunities to prepare for HER2-low. They applied this knowledge to lead projects at their own institutions focusing on the anticipated changes around HER2-low.

Results (if a Case Study enter NA)
The learners identified the following challenges and opportunities: Defining HER2-low: Several learners had heard misconceptions around the definition of HER2-low. Recent studies have defined HER2-low as IHC 1+ or IHC 2+ with ISH-negative. Interobserver concordance with IHC 0 vs 1+: Several learners discussed the challenges around interpreting IHC 0 vs 1+. They felt that some pathologists may need guided feedback to improve their diagnostic skills. Use of IHC vs. ISH: Several learners only performed ISH for HER2 testing on all breast cancer samples. If HER2-low emerges as a third category, they would need to return to IHC. Implications for non-metastatic breast cancer: Recent HER2-low studies have focused on patients with metastatic breast cancer. If HER2-low emerges as a third category, it is unclear whether this designation will also be used in patients who have early-stage breast cancer.

Leadership
As pathologists prepare for HER2-low, they have opportunities to lead projects to assess and improve IHC interobserver concordance, coach others on IHC interpretation, increase operational efficiency, strength communication skills, and build up the team by proactively anticipating challenges around HER2-low.

Conclusion
HER2-low breast cancer may be emerging as a new category. Through a peer-to-peer learning collaborative, pathologists identified ways to proactively prepare and demonstrate leadership so that cancer centers and laboratories may be ready to embrace a new paradigm of HER2 classification in breast cancer.
Reagent Lot Variation Assessment: Establishing the Suitable Acceptability Criteria and Implementing an Efficient and Cost-effective Approach
Authors: Newland P , Asinas J M 
Published: November 2022

Abstract

Introduction/Objective
When reagent lot number change for a particular assay it is hoped that the results obtained from the new lot are comparable with those of the old lot and so will not lead to misleading clinical conclusions based on either the reference intervals or previous results on the same patient. This study has criticality evaluated and compared various methods of establishing reagent lot-to-lot verification acceptability criteria to determine the most suitable approach in Sidra Medicine Clinical Biochemistry Department in order to implement an efficient and cost-effective method of verifying new reagent lot numbers.

Methods/Case Report
Several methods and approach for establishing in-house acceptable criteria for determining reagent variations were critically evaluated. These methods include the use of CLSI EP26-A guidelines, proficiency testing or external quality assessment (EQA) total allowable errors (TeA) and internal quality control (IQC) in-house target SD and CV reflecting the current assay performance. A user friendly statistical template was also produced to be able to improve fhe current workflow, data entry, presentation and documentation of each test with a new reagent lot number approved and implemented for patient testing.

Results (if a Case Study enter NA)
A full version of Reagent Lot Variation Acceptance Table was produced showing comprehensive established criteria based from methods mentioned above. IQC and patient comparability results are entered in an excel template which automatically calculates the differences and shows if the new lot number passed or failed based on the in-house acceptability criteria established. The reagent lot-to-lot verification template is updated each month using complex excel rules to keep the acceptability limits in accordance with the most current in-house IQC target mean and SD based from the most recent monthly IQC reviews.

Conclusion
The comparison of different reagent lot variation acceptability criteria indeed raised awareness of the efficiency and practicality of performing reagent lot-to-lot verification. CLSI EP26-A approach was observed to have the least sample number requirement. However, one patient sample for comparison study seems not enough to justify the approval and implementation of the new reagent lot number to consider the assays AMR. The IQC SD and CAP Total Allowable Error (TeA) acceptability criteria are more effective since there is more number of patient samples used for comparability across the assays AMR.
Validation and Comparison Study for Fourth Generation HIV Test Kit
Authors: Prasai K , Patel D B , Lee H 
Published: November 2022

Abstract

Introduction/Objective
CDC recommends the use of 4th generation HIV test as the first line of screening. Alere Determine HIV – 1/2 Ag/Ab Combo (Abbott Diagnostics Scarborough, Inc., Scarborough, Maine) (Alere) is a qualitative 4thgeneration assay that detects HIV 1/2 antibodies and p24 antigen. In this validation study, Alere was compared with OraQuick Advance Rapid HIV 1/2 Antibody test (OraSure Technologies, Inc., Bethlehem, PA) (Oraquick), a qualitative 3rd generation test and BioPlex (Bio-Rad Laboratories, Hercules, California) a 5th generation test that detects and differentiates between HIV 1 and 2 antibodies and p24 antigen.

Methods/Case Report
Comparison study: Forty-five samples were tested simultaneously on the three assays. Results for the patient samples were confirmed with Geenius (Bio- Rad Marnes-La-Coquette, France) or PCR assays for antibody or antigen positive cases respectively.

Precision study
A HIV-1 antibody positive and an all-negative sample were tested 10 times each to validate the precision of the Alere test.

Dilution study
A positive sample for HIV-1 antibody was used for dilution with a HIV negative serum sample. Diluted samples from 1:10 to 1:1000 were tested using Alere and BioPlex.

Results (if a Case Study enter NA)
Comparison study revealed that sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for Alere test were 100%. Sensitivity for Oraquick was 86.6% and NPV was 77.77%. Specificity and PPV were 100%. BioPlex showed sensitivity and NPV of 100%, but specificity was 78.5% and PPV was 90.90%. Precision study showed reproducible results on the Alere test. Dilution study revealed that Alere assay gave positive results up to 1:300 dilution, and BioPlex assay was positive up to 1:500 dilution.

Conclusion
Our studies showed that Alere had the sensitivity and specificity of 100% making it an effective screening test in acute settings. BioPlex assay demonstrated that it was the most sensitive test with quantitative index for the HIV 1 and 2 antibodies and p24 antigen. Therefore, both Alere and BioPlex tests are good initial screening tests
Clonal Evolution of t(8;21) Coexisting with t(9;22) in a Blastic Transformation of Chronic Myeloid Leukemia
Authors: Deb P Q , Jiang J 
Published: November 2022

Abstract

Introduction/Objective
Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by chromosomal translocation t(9;22) and the production of the fusion protein BCR-ABL1. The clinical course of the disease is characterized by a chronic phase, accelerated phase, and blast phase. One of the criteria for the progress of chronic phase to accelerated phase is the presence of cytogenetic anomaly additional to t(9;22). The blast phase of CML usually presents as acute myelogenous leukemia (AML); however, its characteristics are different from de novo AML. One of the most common subtypes of de novo AML with balanced translocation is AML with t(8;21). Here, we present a case of the blast phase of CML that presents t(8;21).

Methods/Case Report
The peripheral blood from a 51-years-old-man presenting with fatigue and splenomegaly showed leukocytosis, mild anemia, marked neutrophilia with left shift, monocytosis, basophilia, and &lt;1% blasts. Flow cytometry identified an increase in granulocyte events with the left shift. Chromosome studies detected t(9;22) by karyotyping and FISH. BCR-ABL1 transcript was detected at 41.98% on the International Scale by RT-PCR, consistent with chronic myeloid leukemia (CML). The following bone marrow biopsy confirmed a diagnosis of the chronic phase of CML with &lt;5% myeloblasts. After a year of treatment with imatinib, the patient developed marked leukocytosis, anemia, and thrombocytopenia. Flow cytometry detected an immature cell population comprising ~50% of total cells positive for CD117, CD34 (partial), CD13 (dim), and CD33. A few blasts were also positive for cMPO and negative for CD14, CD64, TdT, Glycophorin A, cytoplasmic CD3, CD19, and other markers. BCR-ABL1 transcript was detected at 56.45% on the International Scale by RT-PCR. Chromosome analysis revealed all cells (20/20) exhibiting t(8;21) leading to a fusion between RUNX1 and RUNX1T1 genes with a maintained t(9;22). FISH analysis confirmed t(8;21) and t(9;22). These findings were consistent with a blast phase of CML.

Results (if a Case Study enter NA)
NA

Conclusion
Progression of CML is frequently accompanied by cytogenetic evolution. However, the development of t(8;21) in Ph+ clones is extremely rare. Only six cases have been previously reported. Misidentifying this blast phase of CML (in the absence of a clinical history of the chronic phase of CML) as AML with recurrent genetic abnormalities is a potential pitfall we should be aware of.
Morphological Characteristics of Malignancy in Circulating Tumor Cells (CTCs): A New Approach to Liquid Biopsies Utilizing Affordable Standard Cytology Techniques and the FDA Cleared Parsortix® System
Authors: Barbato C , Rossi E , Kenny C , McCully P , Gray J , Mincer T , Washington J , Mejia Feliz J , Repollet M 
Published: November 2022

Abstract

Introduction/Objective
The process of metastasis is responsible for most cancer deaths. Identification of tumor cells circulating in blood (CTCs) has the potential to offer important information to patients and clinicians regarding disease status, longitudinal monitoring, remission status and assessment of patient prognosis, among others. However, currently CTC tests in the market are expensive and are not covered by medical insurance, making them unaffordable for most cancer patients. Legacy CTC technologies also require the use of expensive immunofluorescence microscopes and reagents, and are not easily implemented in standard clinical laboratory settings, thus preventing their use as standard of care. Onc-ADaPT™ Clinical Laboratories have explored a method to identify CTCs using the FDA cleared Parsortix® System (ANGLE plc, Guildford, UK) followed by standard cytology processing, staining and analysis, significantly reducing the cost of operations and increasing the likelihood of affordability to patients everywhere.

Methods/Case Report
The basic features of malignancy were listed by a Senior Cytologist (CT) and reviewed by another CT. Cancer cell lines were spiked into normal donor blood collected in Streck tubes. Non-spiked healthy volunteer blood was used to establish the background. The samples were then processed through the Parsortix® system producing 200µL suspension of separated cells. The harvest was then processed using Cytospin, stained with standard Pap Stain and reviewed with bright field microscopy by qualified CTs.

Results (if a Case Study enter NA)
Spiked tumor cells were identified and correctly categorized by the Cytologists. Non-spiked normal donor samples were negative for malignancy. Cells of interest were identified in the non-spiked HNV samples and classified as non-malignant (NOS). Using the training set, CTs later analyzed the available patient sample. The positive cancer patient sample showed cells with obvious characteristics of malignancy.

Conclusion
The basic characteristics of malignancy used for analysis of standard cytology specimens are adequate to identify CTCs using the established background to eliminate the NOS cells. CTC testing can be performed using the combination of Parsortix® System, standard cytology staining and analysis by qualified Cytologists.