bluuebunny/crossref_metadata_2025 huggingface dataset:
A case report of type 2M Von Willebrand disease with unique mutations
Authors: Qi Xiaohua , Fang Yanan
Published: November 2022

Von Willebrand disease (vWD) is the most common inherited bleeding disorder. It results from quantitative or qualitative defects of the von Willebrand factor (vWF) protein, and is divided into three types, namely type 1, type 2(2A, 2B, 2M, and 2N), and type 3 vWD. Here we report a case of 55-year-old female who presented with recurrent gastrointestinal bleeding due to angiodysplasia. Her past medical history is significant for vWD (type unknown) with hemoptysis, epistaxis and menorrhagia requiring Humate-P replacement multiple times. She has one sister with mild vWD of unknown type and 4 other siblings with no bleeding history. Coagulation testing shows normal PT and aPTT. Von Willebrand panel shows vWF antigen of 33%, VWF ristocetin cofactor activity of 15%, and Factor VIII of 87%. The ratio (VWF: RCo/VWF: Ag) is low (0.45) and the multimer pattern is normal. This is consistent with type 2M vWD. VWD gene sequencing shows heterozygous variants of c.4241T>G (p.Val1414Gly) and c.5227G>A (p.Val1743Met). Of note, one variant (c.4241T>G/p.Val1414Gly) has been reported in two individuals with type 2A but not in type 2M vWD. This may truly represent different types of vWD caused by same mutation or could be due to variation in testing and/or result interpretation among laboratories. The other variant c.5227G>A(p.Val1743Met) in A3 domain has never been reported with uncertain significance. Further investigation including vWF panel testing and genetic analysis in family members would help characterize those mutations.
Measuring clinical lead testing coverage to support a population health initiative
Authors: Ko Kyungmin , Dowlin Michael , Mroue Youssef , Chong Thomas , Oezguen Numan , Singh Ila
Published: November 2022

Despite national efforts to reduce lead exposure, some children are still exposed to lead, leading to damage to the nervous system, delayed development, and learning and behavioral problems. CDC has recommended targeting high-risk groups for screening. In addition, Texas Department of State Health Services reported a concerning 17% lead testing coverage of 0-to-5-year-olds in in Harris County (where Houston is located). With the eventual goal of improving lead-related clinical care in a large pediatric hospital network, we asked the following questions: 1) What are the high-risk groups specific to our patient population? 2) For patients who are screened positive, are we adequately confirming the results? 3) For those with confirmed lead exposure, are we providing adequate follow-up care? To answer these questions, we analyzed lead testing and hemoglobin testing data on all children less than 6 years of age from the Texas Children’s Hospital’s electronic health record between 2017 and 2021. Lead screening could be performed on capillary or venous blood, but for elevations on capillary blood we analyzed if the results were confirmed with a venous blood test, as recommended by CDC. We used hemoglobin testing as an indicator of follow-up care of lead-exposed children, because an anemia work-up is recommended for such children. We repeated analysis using two different lead level thresholds, because of recent change to the CDC blood lead reference value from 5 mcg/dL to 3.5 mcg/dL in May 2021. We found 273 children (0.33% of children with capillary blood test) to have cBLL = 3.5mcg/dL. There was a significant racial disparity in the rate of lead screening. For example, the screening rate of Black children was 14%, whereas that of White children were 23%. There was a geographic discrepancy between the areas with most elevated cBLL and testing volume. For example, the area where cBLL was most frequently elevated (3.7%) received less than a fifth of tests compared to the most well-tested area. Only 75% of children with a cBLL = 5mcg/dL received a timely venous blood lead test for confirmation, and this dropped to 43% for children with a cBLL = 3.5mcg/dL. Similarly, only 75% of children with a confirmed venous lead level = 5 mcg/dL received a follow-up repeat vBLL test, and 55% received a follow-up hemoglobin measurement. There is room for improvement in population lead health, in terms of both equity and resource distribution. Improvement of lead-related clinical practice could benefit hundreds of children in the Houston metropolitan area.
Patient Outcomes in CMV and SARS-CoV-2 Coinfection
Authors: Walley Debbie
Published: November 2022

This study examines clinical outcomes in patients with cytomegalovirus (CMV) and SARS-CoV-2 coinfection. Between June and November 2020, previously immunocompetent patients with SARS-CoV-2 and CMV coinfection were identified at Houston Methodist Hospital as part of routine clinical correlation by a molecular pathologist. SARS-CoV-2 nasopharyngeal specimens were analyzed by real time reverse-transcriptase polymerase chain reaction (RT-PCR). All CMV tests were performed on plasma or bronchoalveolar lavage (BAL) specimens and analyzed by competitive polymerase chain reaction. 65 previously immunocompetent patients with CMV and SARS-CoV-2 coinfection were identified. Patient demographics include 41 male patients (63%) and 24 female patients (37%) ranging in age from 34 to 86 years (mean: 66.04, median 68). Documented pre-existing conditions include 27 patients with hypertension 41.5%), 19 patients with diabetes mellitus (29.2%), 9 patients with coronary artery disease (13.8%), and 3 patients with asthma (4.6%). Eight patients (12.3%) had no documented pre-existing conditions. The plasma CMV viral load ranged from <300 to 21,566 IU/mL. The CMV PCR results from bronchoalveolar lavage and bronchial wash specimens ranged from <300 to 59,127 IU/mL. CMV PCR was initially negative in 10 patients then positive on serial testing. 60 patients were critically ill requiring ventilator support (92.3%). 47 patients (72.3%) expired, 7 patients (10.8%) were transferred to a long term acute care facility, 3 patients (4.6%) were discharged to a rehabilitation facility, 3 patients (4.6%) were discharged home, and 1 patient (1.5%) remained in-patient at the time of analysis. The prevalence of CMV seropositivity and medical comorbidities increases with age. Reactivation of latent CMV is a known occurrence in critically ill patients that is associated with poor outcomes. The majority of the patients in our cohort were 50 years old, and all were severely to critically ill with a mortality rate of 72.3% These findings suggest CMV portends a worse prognosis in patients with COVID-19. These findings also demonstrate the importance of clinical correlation in molecular testing.
MECOM copy number alterations identify a new group of myeloid neoplasms with a poor prognosis
Authors: Yang David , Karlin Kirill , Bryke Christine , Michaels Phillip
Published: November 2022

Objective

Myeloid neoplasms (MNs) harboring inv(3)(q21q26)/t(3;3)(q21;q26) or MECOM gene rearrangements as identified by fluorescence in situ hybridization (FISH) are known to carry a poor prognosis. The objective of this study is to assess prognostic impact of MNs with copy number alterations (CNA) in MECOM as compared to MNs with inv(3)/t(3;3) or MECOM rearrangements. We present those initial comparative results and secondarily assess whether genetic mutations that confer a worse clinical outcome are also associated with MNs with MECOM CNA.

Methods

A retrospective review of electronic pathology records was performed at Beth Israel Deaconess Medical Center. All MNs from 2016 – current with MECOM FISH (Abbott Molecular, Abbott Park, IL) confirmed analyses were extracted. Other additional items extracted included karyotype and next-generation sequencing (NGS) results of a 65 gene myeloid panel (SmartGenomics Myeloid Profile, PathGroup, Nashville, TN). Kaplan-Meier and ANOVA were performed using GraphPad Prism (San Diego, CA).

Results

A total of 307 cases were identified in which MECOM FISH was performed. Exclusion of cases lacking inv(3)/t(3;3), MECOM rearrangement, or MECOM CNA provided an initial study cohort of 20 cases. 5 cases had MECOM rearrangement with inv(3)/t(3;3), 7 had MECOM rearrangement without inv(3)/t(3;3), and 8 had MECOM CNA. 13 of 20 cases had a complex karyotype, 13 of 20 cases had a monosomal karyotype, 10 of 20 cases had both a complex and monosomal karyotype. Of the 20 cases in which MECOM FISH demonstrated inv(3)/t(3;3), MECOM rearrangement, or CNA, NGS was performed on 16 cases. Genes known to be associated with a significant negative overall survival (OS) include ASXL1, EZH2, IDH2, KRAS, NRAS, RAD21, RUNX1, SRSF2, STAG2, TP53 with single and multiple mutations found in 9 of 20 cases. Kaplan-Meier analysis revealed no significant difference in OS among the three MECOM aberration groupings (Log-rank test; p=0.77). Single factor ANOVA analysis revealed enrichment for high risk gene mutations in MECOM CNA (p=0.04) and TP53 mutations (p=0.04) when compared to MNs with MECOM rearrangements.

Our analysis of MNs with MECOM aberrations by FISH reveal that MECOM with CNA display similarly poor overall survival as MNs with inv(3)/t(3;3) and MECOM rearrangements. Additionally, the MECOM CNA group was enriched for high risk gene mutations and TP53 as compared to inv(3)/t(3;3) and MECOM rearrangement groups. Overall, the initial results of this study reveal a new group of MNs harboring MECOM CNA that confer a poor prognosis and high risk mutational profile.
Barotrauma in a Previously Healthy and Young COVID-19 Patient: an Autopsy Case Report
Authors: Kadow Z , Wilken N , Gallardo J , Xu Y
Published: November 2022

Introduction/Objective

Since the emergence of a novel SARS-CoV-2 virus caused coronavirus disease 2019 (COVID-19), a great number of autopsy studies have been published. However, histopathologic studies focused on pulmonary barotrauma are very rare. Here we report an autopsy confined to the lungs on a young COVID-19 patient.

Methods/Case Report

The patient was a 37-year-old male, non-smoker, with no significant past medical history, and a body mass index of 24.1, who presented with shortness of breath and cough. A computerized tomography (CT) showed features of atypical pneumonia. The main abnormal laboratory data included elevated partial thromboplastin time, fibrinogen, and D-Dimer. The patient had been on mechanical ventilation for 35 days, and was complicated by recurrent pneumothoraces, hypotension, and worsening hypoxia. An autopsy limited to the lungs was performed after the patient expired. Grossly, the lungs showed increased weight, adhesions on visceral pleural surface, patchy consolidation and dilated subpleural cysts. Histological examination revealed cystically dilated/remodeled airspaces with extensive coagulative necrosis, focal alveolar hemorrhage and edema, focal confluent fibrosis, and subpleural blebs. Fresh fibrinous thrombi were seen in small- and medium-sized vessels. Viral cytopathic changes or significant inflammation were not observed. The findings in the lungs were consistent with barotrauma in COVID-19.

Results (if a Case Study enter NA)

NA.

Conclusion

This case demonstrates various histopathologic changes of the lungs in a previously healthy and young COVID-19 patient with prolonged hospital course of mechanical ventilation. The features of diffuse alveolar damage with inflammation usually seen in the early stage of barotrauma are not identified. Our findings in the lungs may represent the histopathologic characteristics of the later stage of barotrauma in COVID-19.
Pseudogout Causing Thoracic Outlet Syndrome
Authors: Abraham A , Duke W
Published: November 2022

Introduction/Objective

Calcium pyrophosphate dihydrate (CPPD) crystal deposition or pseudogout is a common entity encountered in routine practice. However, when a common entity presents in uncommon locations with unusual clinical manifestations, it creates a diagnostic conundrum. Pseudogout commonly occurs in the joint extremities including knee, wrist, shoulder, hip, and ankle joints. The sternoclavicular joint is a rare site for pseudogout with very low incidence. To the best of our knowledge, there are only two other cases of pseudogout mimicking a tumor causing vascular obstruction in the literature.

Methods/Case Report

A 63 year old male presented with an enlarging supraclavicular mass. A computed tomography angiography scan of the chest revealed an irregular soft tissue mass located behind the medial clavicle measuring up to 4 cm and was noted to compress and partially occlude the right subclavian vein. Partial occlusion of right axillary vein, right internal jugular vein, and right brachiocephalic vein were also noted on imaging. The venous compression led to outflow obstruction and resultant recurrent deep vein thrombosis of the right upper extremity. Due to compression by the mass, he required stenting of the right subclavian vein which unfortunately reoccluded. Subsequently, the patient underwent excision of the mass and partial resection of the first rib with decompression of the thoracic outlet. The excisional biopsy revealed dense rhomboid-shaped CPPD crystal depositions in irregular nodules within a background of fibrinoid material and fragments of unremarkable cartilaginous tissue. The patients compressive symptoms were relieved following the excision. While clinically and radiologically the mass was concerning for a malignant tumor, histological examination provided a definitive diagnosis of a benign process.

Results (if a Case Study enter NA)

NA.

Conclusion

Pseudogout is a rare mimicker of bone and soft tissue tumors and differentiation from an enchondroma, or grade 1 chondrosarcoma becomes a challenge especially on small tissue biopsies and is a possible diagnostic pitfall.
Systemic and Local Disease Manifestations Following COVID-19 Vaccination
Authors: Mahalingam V D , Huang J Z , Bernacki K D , Amin M B , Zhang P
Published: November 2022

Introduction/Objective

COVID-19 vaccine-related lymphadenopathy, particularly in the ipsilateral axilla, is a relatively well-known side effect of mRNA vaccines with many reports in radiology, but less is known regarding histopathology and additional sites of lymphadenopathy, as well as other localized potential vaccine-related mass manifestations. In addition to a case of minimal change disease, we report two cases here with associated systemic and local pathologic changes related to COVID-19 vaccination.

Methods/Case Report

In case #1, a 17-year-old male presented with a 2.4 cm left postauricular mass. He had originally noticed the mass six months prior and thought that it had recently been growing. The mass was soft, nonfluctuant, and nontender to palpation. Given the risk of malignancy, a resection was performed. Histology showed an enlarged lymph node composed of mixed inflammatory cell components consistent with lymphoid hyperplasia and no evidence of malignancy. On further chart review, the patient had received his second COVID-19 vaccination just prior to noticing the mass enlarging. A SARS-CoV-2 Anti-Spike IgG assay was as high as 24,396 AU/ml, suggesting that this benign lymphadenopathy was most likely related to his vaccination. For case #2, a 47-year-old male developed a painless right deltoid mass shortly after receiving his vaccination at the same area that subsequently increased in size over seven months to 6.5 cm. Imaging showed a heterogeneous mass within the deltoid muscle concerning for malignancy and a biopsy was performed. Sections showed wavy, bland spindle cells with nuclei staining diffusely positive for beta-catenin, consistent with fibromatosis at his vaccination site.

Results (if a Case Study enter NA)

NA.

Conclusion

In summary, these case reports show potential systemic and local reactive effects in response to COVID-19 vaccination.
A Rare Case of Primary Cardiac Undifferentiated Pleomorphic Sarcoma with Brain Metastases
Authors: Monika F , Groh D
Published: November 2022

Introduction/Objective

Undifferentiated pleomorphic sarcomas are highly malignant undifferentiated fibroblastic tumors with an aggressive clinical course. Primary cardiac undifferentiated pleomorphic sarcomas are extremely rare (incidence < 0.1%) and most commonly occur in the left atrium. We report a case of a left atrial undifferentiated pleomorphic sarcoma that was thought to be a cardiac myxoma on imaging studies.

Methods/Case Report

A 22-year-old female without past medical or family history presented to the emergency department for a cerebrovascular accident. During clinical work up, transesophageal echocardiogram revealed a 3 cm mass attached to left atrial septum and a 1.8 cm mass attached to the interatrial septum with associated thrombus formation. The patient underwent surgical excision of the mass. Histological analysis revealed a tumor comprised of spindle and epithelioid cells with abundant nuclear atypia, mitotic figures, and necrosis. Extensive immunohistochemical analysis did not show specific lineage and the tumor was classified as an undifferentiated pleomorphic sarcoma. Two months after initial surgery, the patient presented with additional neurologic deficits and brain lesions. The pathologic findings in the brain biopsy specimen were identical to those in the cardiac specimen and consistent with metastatic undifferentiated pleomorphic sarcoma. This case provides insight into the metastatic behavior of high-grade cardiac sarcomas and their unusual clinical and radiographic presentations, including neurologic manifestations that are unique to the primary cardiac location of the tumor.

Results (if a Case Study enter NA)

NA

Conclusion

In conclusion, because the majority of cardiac undifferentiated pleomorphic sarcomas occur in the left atrium, these growths can be mistakenly diagnosed as benign myxoma preoperatively. This case provides insight into the metastatic behavior of high-grade cardiac sarcomas and their unusual clinical and radiographic presentations, including neurologic manifestations that are unique to the primary cardiac location of the tumor.
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

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

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

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

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

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

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

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

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

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 <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 <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

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.
Rare Case of Distant Cutaneous Metastasis of Urothelial Carcinoma
Authors: Htoo A , George R S , Lin G
Published: November 2022

Introduction/Objective

Cutaneous metastasis of urothelial carcinoma is extremely rare with poor prognosis. Many cutaneous metastases present in locoregional areas such as abdomen, groin, genitalia or thigh. Only very few cases present with distant cutaneous metastases. We report a rare case of urothelial carcinoma presenting with a cutaneous metastasis to the right neck.

Methods/Case Report

A 71-year-old male with a history of prostate cancer in 2009 presented with hematuria with clots, urinary retention and dysuria. The patient was also noted to have right submandibular ulcerative mass measuring 2.6 cm. Cystoscopy revealed a nodular tumor in the right lateral trigone area and transurethral resections of bladder tumor revealed high-grade papillary urothelial carcinoma, invasive into muscularis propria with lymphovascular invasion. Skin punch biopsy of the right submandibular mass was obtained revealing an infiltrative nodular proliferation of sheets of atypical epithelioid cells with readily identifiable mitoses in at least the dermis without an epidermal connection. Immunostains show the lesional cells are positive for CK5/6, EMA, Ber-EP4 (weak), p40, and GATA3 with variable positivity for p16, consistent with metastatic urothelial carcinoma. The patient received 4 cycles of cisplatin-gemcitabine chemotherapy with good partial response, continued with avelumab for maintenance therapy and is alive up to 6 months.

Results (if a Case Study enter NA)

NA.

Conclusion

Most cutaneous metastases of urothelial carcinoma occur in the local region and have poor prognosis with patients dying within several weeks without treatment. It is important for pathologists to be aware of cutaneous metastatic urothelial carcinoma in more distant sites.
Incidental Thyroid Carcinomas versus Benign Thyroid Cases. A Clinico-Radiological Comparison
Authors: Irfan A , Khalaf Z , Hamidpour S , Abbasi S
Published: November 2022

Introduction/Objective

We aim to identify the clinico-radiological characteristics unique to incidental thyroid carcinomas (ITCs) in comparison to benign thyroid cases. Previous studies show a positive correlation between ITCs and a euthyroid state. Currently nodules greater than 4 cm (N>4cm) with or without a negative fine needle aspiration (FNA) are excised because of a higher risk of malignancy.

Methods/Case Report

A 6-year retrospective study was performed on 227 thyroidectomy specimens collected during 2017-2022. 146 patients were benign. 26 patients with a negative/absent FNA were found to have ITCs. 55 patients had malignant thyroids (MTs). Age, gender, compressive symptoms, thyroid hormone status, presence of nodules, number of nodules, N>4cm, suspicious radiologic findings, personal history of other malignancies, family history of thyroid cancer (FHTCA) and a family history of thyroid disease were analyzed between the benign and ITC groups. A t-test was utilized for numerical variables and a chi-square test for categorical values. For any significant correlations, a maximum likelihood estimate was used to calculate the odds ratio.

Results (if a Case Study enter NA)

Incidence of ITC amongst all specimen was 11.4% (26/227). 32% (26/81) of all reported MTs were ITCs. Papillary thyroid carcinomas accounted for 92.3% (24/26) of ITCs, follicular carcinomas accounted for 7% (2/26). 3/26 patients with ITC, 4/146 patients with benign thyroids and 5/55 patients with MT had a FHTCA. We found a significant correlation between FHTCA and thyroid malignancy [MT + ITC; odds ratio = 4.11 (CI = 1.198 – 14.154)]. A FHTCA was associated with more than a 4 times likelihood of having ITC compared to those without a family history (odds ratio = 4.77) (CI [1 - 22.782]). Other variables did not show any statistically significant differences between the ITC and benign groups.

Conclusion

Although previous studies report a correlation between ITCs and a euthyroid status and N>4cm, our study didn’t confirm it. However, this may be due to our smaller sample size. In our patient population, an FHTCA was associated with significantly higher incidence of ITCs which may outline a subpopulation that should be considered for more aggressive screening. No other variables were statistically significant.
The eyes don't see, what the mind doesn't know
Authors: Elsarraj H , Hamza A
Published: November 2022

Introduction/Objective

Calcifying fibrous tumor is a rare benign mesenchymal neoplasm. The etiology and pathogenesis of this tumor are uncertain. It has wide anatomical distribution. The tumor is most commonly found in the soft tissues of the extremities in younger individuals. However, in middle aged patients it tends to affect the visceral locations more commonly. In visceral location it can mimic aggressive lesions clinically. The purpose of this report is to describe a case of calcifying fibrous tumor in a 71-year-old female with a history of breast carcinoma who was found to have an incidental small bowel mass on her follow up. Clinically and radiologically and the main diagnostic consideration were metastatic disease and gastrointestinal stromal tumor.

Methods/Case Report

The patient underwent an open small bowel resection, and a 6.5 cm segment of small bowel was sent to pathology. Grossly, a 2.0 cm tan-pink smooth round submucosal polyploid mass protruding into the lumen, mimicking gastrointestinal stromal tumor was identified. The tumor was hard and serially sectioned to reveal a white, calcified cut surface. Microscopically, the tumor appeared hypocellular and composed of scant spindle cells embedded in a dense, hyalinized and calcified, collagenous stroma. Immunohistochemical stains for pan cytokeratin, DOG1, desmin, S100, CD34, and MUC4 were negative, and diagnosis of calcifying fibrous tumor was rendered.

Results (if a Case Study enter NA)

NA.

Conclusion

This case highlights the importance of knowledge of rare entities in providing accurate diagnosis for lesions that can clinically mimic common tumors.