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Article: Molecular analysis with pancreaseq® in evaluation and management of pancreatic cysts: A cohort of 28 patients.

Ardor, Gokce Deniz / Hanna, Helena / Ozalp, Bora / Nassar, Aziza

2023 Volume 20, Page(s) 23

Abstract: Objectives: Herein, we present the PancreaSeq® results of 28 patients and emphasize the usefulness of molecular testing in evaluation of pancreatic cysts.: Material and methods: A total of 10 (35.7%) non-diagnostic, 6 (21.4%) negative, 5 (17.8%) ... ...

Abstract	Objectives: Herein, we present the PancreaSeq® results of 28 patients and emphasize the usefulness of molecular testing in evaluation of pancreatic cysts. Material and methods: A total of 10 (35.7%) non-diagnostic, 6 (21.4%) negative, 5 (17.8%) atypical, and 7 (25%) were positive for mucinous cystic neoplasm (MCN) pancreatic cyst aspirates were analyzed with PancreaSeq® at Mayo Clinic, Jacksonville between September 2021 and February 2023. Results: Three non-diagnostic, two negative, three atypical, and two positive for MCN cysts were positive for KRAS and GNAS mutations. They were interpreted as intraductal papillary mucinous neoplasm (IPMN) with low risk for progression to high-grade dysplasia/adenocarcinoma. One negative case was positive for KRAS and GNAS mutation and RNF43 copy number alteration. It was interpreted as IPMN with a low risk of progression. Two non-diagnostic, one negative, and two positive for MCN cysts were positive for KRAS mutation. All were interpreted as IPMN/MCNs with low risk of progression. One positive for MCN case was positive for GNAS mutation and ALK fusion and one positive for MCN case was positive for GNAS mutation, ALK fusion, and RNF43 copy number alteration. Both were interpreted as IPMN and their risk of progression was interpreted as not well understood. One atypical case was positive for KRAS and TP53 mutation and was interpreted as IPMN/ MCNs with a high risk of progression. VHL mutation was present in one non-diagnostic case. It was interpreted as serous cystadenoma and the risk for progression was low. Conclusion: Molecular analysis of pancreatic cysts with PancreaSeq® is useful in accurate diagnosis, especially when cytologic material is non-diagnostic and helps improve patient management.
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2158838-7
ISSN	1742-6413 ; 0974-5963
ISSN (online)	1742-6413
ISSN	0974-5963
DOI	10.25259/Cytojournal_28_2023
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Article ; Online: First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non-Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case Report.

Majeed, Umair / Li, Shenduo / Seegobin, Karan / Nassar, Aziza / Manochakian, Rami / Zhao, Yujie / Lou, Yanyan

JTO clinical and research reports

2023 Volume 4, Issue 7, Page(s) 100536

Abstract: ALK-EML4 fusion-positive lung adenocarcinomas (LUADs) are effectively treated with ALK tyrosine kinase inhibitors, but most patients eventually develop resistance to these drugs owing to ALK-dependent or independent mechanisms. Endothelial to mesenchymal ...

Abstract	ALK-EML4 fusion-positive lung adenocarcinomas (LUADs) are effectively treated with ALK tyrosine kinase inhibitors, but most patients eventually develop resistance to these drugs owing to ALK-dependent or independent mechanisms. Endothelial to mesenchymal transformation with SCLC development is an ALK-independent mechanism of resistance that has not been previously reported with sequential ALK I1171T mutation while the patient is on treatment for the SCLC. Here, we report the first case of sequential SCLC transformation followed by ALK I1171T mutation in a patient with ALK-EML4 fusion-positive LUAD. After progression on multiple lines of therapy, we describe our experience of managing ALK-mutant LUAD and transformed SCLC with a novel combination of lorlatinib and temozolomide. We also briefly summarize cases of endothelial to mesenchymal transformation ALK-mutant LUAD from the literature.
Language	English
Publishing date	2023-06-15
Publishing country	United States
Document type	Case Reports
ISSN	2666-3643
ISSN (online)	2666-3643
DOI	10.1016/j.jtocrr.2023.100536
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Article: Two unique cases of metastatic malignant melanoma of the gastrointestinal tract.

Ahmed, Momin / Ardor, Gokce Deniz / Hanna, Helena / Alhaj, Ahmed M / Nassar, Aziza

International journal of surgery case reports

2023 Volume 103, Page(s) 107907

Abstract: Introduction and importance: Gastrointestinal tract (GIT) is a common site for malignant melanoma metastasis, with small bowel being the most common. It is usually difficult to diagnose at an early stage because of the anatomical location of the disease. ...

Abstract	Introduction and importance: Gastrointestinal tract (GIT) is a common site for malignant melanoma metastasis, with small bowel being the most common. It is usually difficult to diagnose at an early stage because of the anatomical location of the disease. It is also challenging for pathologists to diagnose due to the small amount of biopsy samples. Survival rates of melanoma patients with distant metastasis are very poor. Case presentation: This study presents two males, aged 67 and 69 years old, who have metastatic melanoma within the GIT. One was metastasis to the esophagus and another with metastasis to the jejunum presenting as intraluminal masses. Their clinical history and pathologic features of the metastasis are evaluated to give an insight into this disease. Clinical discussion: Gastrointestinal melanoma is hard to detect due to its anatomical location and limited ability to biopsy. Typically, they present at an advanced stage when diagnosed. Approximately 60 % of patients with cutaneous melanoma will have GIT metastasis at the time of autopsy. The small bowel was found to have an affinity for malignant melanoma due to the expression of the CCR9 ligand, CCL25. BRAF mutations are much less observed in GIT mucosal melanomas as compared to cutaneous melanomas. Furthermore, AKAP13-NTRK3 fusion has been reported specifically in the GIT mucosal melanomas. NTRK fusions in general can be observed in metastatic melanomas and have been reported in GIT metastatic melanomas. Conclusion: GIT malignant melanomas are difficult to detect due to their anatomical location, with poor prognosis, and have a unique genetic profile.
Language	English
Publishing date	2023-02-03
Publishing country	Netherlands
Document type	Case Reports
ISSN	2210-2612
ISSN	2210-2612
DOI	10.1016/j.ijscr.2023.107907
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Article ; Online: Oncotype DX and Prosigna in breast cancer patients: A comparison study.

Abdelhakam, Dina A / Hanna, Helena / Nassar, Aziza

Cancer treatment and research communications

2021 Volume 26, Page(s) 100306

Abstract: Background: Oncotype Dx® (ODX) is the most used prognostic and predictive assay for ER + breast cancer (BCa) and is categorized into low (< 18), intermediate (18 to 30), or high (≥31) risk of recurrence. Prosigna® is a prognostic signature to estimate ... ...

Abstract	Background: Oncotype Dx® (ODX) is the most used prognostic and predictive assay for ER + breast cancer (BCa) and is categorized into low (< 18), intermediate (18 to 30), or high (≥31) risk of recurrence. Prosigna® is a prognostic signature to estimate distant recurrence-free survival for stage I/II, ER+ cancer in postmenopausal women treated with adjuvant therapy. The goal of the study is to assess the agreement between ODX and Prosigna®. Materials and methods: 100 previously ODX classified peri and postmenopausal, early-stage (I or II) BCa patients were retrieved and Prosigna assay was performed on archived tumor blocks on a NanoString nCounter® DX Analysis System. Results: ODX assay was assigned as follows: 57% low, 39% intermediate, and 4% high. There were 8% two-step disagreements (high to low or vice versa) between ODX and Prosigna®; and 42% one-step disagreement (low to intermediate or vice versa). 78% were classified by Prosigna as luminal A and 22% as luminal B. The majority of luminal A cases (67/78; 85.9%) had low ROR score whereas ODX classified almost two-thirds (50/78~ 64%) as low RS. An insignificant percentage of luminal B cases (1/22 - 4.5%) were classified as high RS by ODX, and a modest percentage were classified as high ROR by Prosigna (15/22 ~68%). According to our follow up results, recurrence was detected in three cases. In all three cases; Prosigna was a better indicator of recurrence. Conclusions: The agreement between ODX and Prosigna® is low, and this has management implications, especially when chemotherapy is needed.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics ; Breast Neoplasms/mortality ; Breast Neoplasms/therapy ; Clinical Decision-Making/methods ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression Profiling/instrumentation ; Genetic Testing/instrumentation ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/prevention & control ; Predictive Value of Tests ; Prognosis ; Reagent Kits, Diagnostic ; Risk Assessment/methods
Chemical Substances	Reagent Kits, Diagnostic
Language	English
Publishing date	2021-01-07
Publishing country	England
Document type	Comparative Study ; Journal Article
ISSN	2468-2942
ISSN (online)	2468-2942
DOI	10.1016/j.ctarc.2021.100306
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Article ; Online: Risk of malignancy assessment of the different cytologic categories in respiratory cytology samples according to the new guidelines of the Papanicolaou Society of Cytopathology.

Ardor, Gokce Deniz / Ahmed, Momin / Hanna, Karina / Ibanoglu, Onur / Nassar, Aziza

Diagnostic cytopathology

2023 Volume 52, Issue 1, Page(s) 16–21

Abstract: Background: Cytology is extremely important for diagnosis of lung carcinoma and the Papanicolaou Society of Cytopathology (PSC) had proposed a new classification system for respiratory cytology for better communication between physicians and better ... ...

Abstract	Background: Cytology is extremely important for diagnosis of lung carcinoma and the Papanicolaou Society of Cytopathology (PSC) had proposed a new classification system for respiratory cytology for better communication between physicians and better patient management. The objective of this study is to analyze our samples in accordance with this classification and to evaluate the diagnostic accuracy of various cytologic techniques and to assess the risk of malignancy. Methods: Eight hundred and twenty respiratory cytology specimens (FNA, BAL, washing, brushing, sputum) collected between 2019 and 2022 were classified according to the PSC system and the risk of malignancy was assessed for each category using follow-up surgical samples. Sensitivity, specificity, and accuracy rates were determined based on a categorial approach, according to a similar study. Results: The data of 820 respiratory cytology specimens from 576 patients were analyzed. 2.6% of these were non-diagnostic, 64.1% were NM, 5% were AC, 0.4% were N-B-LG, 4% were SM and 23.9% were ML. The risk of malignancy for each diagnostic category were: 42.8% for non-diagnostic, 31.2% for NM, 43.9% for AC, 87.9% for SM, 94.3% for ML. Sensitivity and specificity was calculated using only the malignant cases considered as positive tests and was 45.57% and 97.34% respectively. Conclusion: Our results correlated with the PSC system, and it was considered useful in clinical practice. However, more studies should be performed to evaluate the usefulness of this system. The ROMs of each category and the impact of different techniques should be further studied.
MeSH term(s)	Humans ; Societies, Medical ; Cytodiagnosis/methods ; Lung Neoplasms/diagnosis ; Lung Neoplasms/pathology ; Sensitivity and Specificity
Language	English
Publishing date	2023-10-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	632710-2
ISSN	1097-0339 ; 8755-1039
ISSN (online)	1097-0339
ISSN	8755-1039
DOI	10.1002/dc.25234
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Article ; Online: Evaluating Low HER2 Status in Invasive Breast Carcinoma via HER2 Immunohistochemistry, with HER2 FISH Correlation: A Cohort of 112 Patients.

Ardor, Gokce Deniz / Komforti, Miglena K / Hanna, Helena / Ibanoglu, Onur / Lochala, Abigail / Nassar, Aziza

The breast journal

2023 Volume 2023, Page(s) 9725647

Abstract: Introduction: Recent trials demonstrated clinically significant benefits in HER2-nonamplified breast cancer with HER2-low expression using novel anti-HER2 antibody-drug conjugates. Thus, HER2-low breast cancer was proposed as a separate diagnostic ... ...

Abstract	Introduction: Recent trials demonstrated clinically significant benefits in HER2-nonamplified breast cancer with HER2-low expression using novel anti-HER2 antibody-drug conjugates. Thus, HER2-low breast cancer was proposed as a separate diagnostic entity. Herein, we reclassify HER2-negative cancers according to the new HER2-low category using a modified system and further investigate HER2-very-low expression. Methods: 114 HER2 immunohistochemistry (IHC)-negative invasive breast tumors were identified from the pathology database of Mayo Clinic, Jacksonville, FL, between January 2019 and August 2022. Two blinded breast pathologists (BP) independently rescored HER2 IHC slides at 200x and 400x magnification. Discordant cases between the two BPs were rescored together. The most recent 2018 ASCO/CAP HER2 scoring criteria were used. HER2 (0) was subdivided into HER2 (absent) and HER2 (very low). HER2 FISH testing was performed in all cases. Results: The cohort comprised of 38 (33.3%) HER2 (0) and 76 (66.7%) HER2 (1+) tumors. The first round of rescoring at 200x and 400x magnification resulted in 17 (14.9%) HER2 (absent), 31 (27.2%) HER2 (very low), and 64 (56.2%) HER2 (1+) and 2 (1.8%) HER2 (2+) tumors by BP1 and 20 (17.5%) HER2 (absent), 33 (28.9%) HER2 (very low), and 61 (53.5%) HER2 (1+) tumors by BP2. The combined final rescoring by BP1 and BP2 was as follows: 15 (13.2%) HER2 (absent), 35 (30.7%) HER2 (very low), 63 (55.3%) HER2 (1+), and 1 (0.9%) HER2 (2+) cases. A comparison of the first round of rescoring between two BPs showed substantial agreement with Cohen's kappa value of 0.67. Both comparisons of first rescoring by BP1 and by BP2 to combined final rescoring showed almost perfect agreement with Cohen's kappa value of 0.83.Follow-up FISH studies showed one amplified tumor. Conclusion: Our data support the need for finer granularity, classification, and understanding of HER2-low breast cancers. We also show that reproducibility between trained BP can be obtained, albeit with scoring at high power and low threshold for showing challenging interpretations.
MeSH term(s)	Humans ; Databases, Factual ; Immunohistochemistry ; Reproducibility of Results ; Breast Neoplasms/diagnosis ; Breast Neoplasms/genetics
Chemical Substances	ERBB2 protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-08-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1289960-4
ISSN	1524-4741 ; 1075-122X
ISSN (online)	1524-4741
ISSN	1075-122X
DOI	10.1155/2023/9725647
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Article ; Online: Utility of p16 and HPV testing in oropharyngeal squamous cell carcinoma: An institutional review.

Abdelhakam, Dina A / Huenerberg, Katherine A / Nassar, Aziza

Diagnostic cytopathology

2020 Volume 49, Issue 1, Page(s) 54–59

Abstract: In the US, 60% to 80% of oropharyngeal squamous cell carcinomas (OPSCCs) are associated with human papillomavirus (HPV). However, until recently, no consensus existed about when and how to test for HPV in patients with head and neck cancers. We aimed to ... ...

Abstract	In the US, 60% to 80% of oropharyngeal squamous cell carcinomas (OPSCCs) are associated with human papillomavirus (HPV). However, until recently, no consensus existed about when and how to test for HPV in patients with head and neck cancers. We aimed to evaluate the use of p16 and HPV testing at our institution because p16 immunohistochemistry is reportedly a reliable surrogate marker for HPV detection in OPSCCs. Methods: We identified all cases at our institution of primary or metastatic squamous cell carcinoma (SCC) of the head and neck with a concurrent p16 immunostain analysis from January 1, 2013, through August 31, 2018. Patient demographic data, tumor characteristics, p16 result, and any HPV result (in situ hybridization and E6 and E7 RNA test) were captured. Results: We identified 104 patients. Most primary tumors (53/57 [93.0%]) and metastases (40/47 [85.1%]) were positive for p16. Thirty-seven cases (35.6%) had reflex high-risk HPV (HR HPV) testing performed. Of the 35 p16-positive cases, 6 had discrepant HR HPV results (p16 Conclusion: p16 immunohistochemistry accurately identifies HPV-positive OPSCC. Cytology specimens have an important role in characterizing SCC of unknown origin. HR HPV testing is not routinely required, and results may be discrepant with p16 findings.
MeSH term(s)	Aged ; Aged, 80 and over ; Alphapapillomavirus/genetics ; Biomarkers, Tumor/genetics ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/virology ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Female ; Human Papillomavirus DNA Tests/methods ; Humans ; Lymph Nodes/virology ; Male ; Middle Aged ; Oropharyngeal Neoplasms/genetics ; Oropharyngeal Neoplasms/virology ; Papillomavirus Infections/genetics ; Papillomavirus Infections/virology ; RNA, Viral/genetics
Chemical Substances	Biomarkers, Tumor ; Cyclin-Dependent Kinase Inhibitor p16 ; RNA, Viral
Language	English
Publishing date	2020-08-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	632710-2
ISSN	1097-0339 ; 8755-1039
ISSN (online)	1097-0339
ISSN	8755-1039
DOI	10.1002/dc.24593
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Article ; Online: Core needle biopsy versus fine needle aspiration biopsy in breast--a historical perspective and opportunities in the modern era.

Nassar, Aziza

Diagnostic cytopathology

2011 Volume 39, Issue 5, Page(s) 380–388

Abstract: Breast fine-needle aspiration biopsy (FNAB) by palpation is on the decline, due to its limitations in diagnostic accuracy, decreased sensitivity, and its replacement with core needle biopsy (CNB). Despite its decreasing utility, superficial fine-needle ... ...

Abstract	Breast fine-needle aspiration biopsy (FNAB) by palpation is on the decline, due to its limitations in diagnostic accuracy, decreased sensitivity, and its replacement with core needle biopsy (CNB). Despite its decreasing utility, superficial fine-needle aspiration (FNA) in breast is still the main modality for evaluating metastatic lesions, recurrence, and axillary lymph node metastasis. New modalities including proteomic pattern expression and methylation profiling of breast lesions are other promising techniques that can be used as ancillary tests for refining the diagnosis of breast lesions using FNAB. Image-guided breast FNA proves to be a successful alternative with high sensitivity and specificity. In this review, the advantages, disadvantages, and inherent limitations of breast FNA and CNB, and new advanced techniques are discussed.
MeSH term(s)	Biopsy, Fine-Needle/methods ; Biopsy, Fine-Needle/trends ; Biopsy, Needle/methods ; Biopsy, Needle/trends ; Breast/pathology ; Breast Neoplasms/diagnosis ; Breast Neoplasms/diagnostic imaging ; Female ; Humans ; Pathology, Surgical ; Surgery, Computer-Assisted/methods ; Ultrasonography, Mammary
Language	English
Publishing date	2011-05
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Review
ZDB-ID	632710-2
ISSN	1097-0339 ; 8755-1039
ISSN (online)	1097-0339
ISSN	8755-1039
DOI	10.1002/dc.21433
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Article ; Online: HER2 testing across practices-Have we come to a consensus on the ideal method of testing? A systematic literature review.

Nassar, Aziza / Pooja, Advani / Chivukula, Mamatha

The breast journal

2020 Volume 26, Issue 6, Page(s) 1185–1188

Abstract: Human epidermal growth factor (HER2) is an oncogene that codes for HER2 protein. The gene is amplified, and protein is overexpressed in 20% of patients and carries a poor prognosis. HER2-positive tumors tend to be more aggressive and highly proliferative. ...

Abstract	Human epidermal growth factor (HER2) is an oncogene that codes for HER2 protein. The gene is amplified, and protein is overexpressed in 20% of patients and carries a poor prognosis. HER2-positive tumors tend to be more aggressive and highly proliferative. In 2006, trastuzumab, a monoclonal antibody targeting HER2, was approved for use with chemotherapy as an adjuvant treatment for women with HER2-positive breast cancer. The drug has shown improved survival rates for women with HER2-positive breast cancer. As promised for survival in HER2-positive patients continues with new research, and as novel drug approvals emerge, HER2 assessment plays a significant role in adjuvant and in metastatic setting. HER2 assays approved by the US Food and Drug administration include immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and bright field dual in situ hybridization (DISH). Accuracy of HER2 testing across laboratories has an impact on treatment as false-negative testing can deprive the patients of trastuzumab therapy. The current review will focus on the variability of HER2 testing across laboratories and the potential impact on treatment.
MeSH term(s)	Antibodies, Monoclonal, Humanized ; Biomarkers, Tumor ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Consensus ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Receptor, ErbB-2/genetics ; Trastuzumab/therapeutic use
Chemical Substances	Antibodies, Monoclonal, Humanized ; Biomarkers, Tumor ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2020-05-12
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	1289960-4
ISSN	1524-4741 ; 1075-122X
ISSN (online)	1524-4741
ISSN	1075-122X
DOI	10.1111/tbj.13867
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Article: A rare case of BK virus non-hemorrhagic cystitis following lung transplant.

David, Justin / Baird, Bryce A / Nassar, Aziza / Geldmaker, Laura / Broderick, Gregory A

Urology case reports

2022 Volume 45, Page(s) 102263

Abstract: BK virus cystitis is known to occur following hematopoietic stem cell transplant (HSCT), but few cases exist in the literature following lung transplant. Because of the rarity of this presentation, patients may have missed diagnoses and prescribed ... ...

Abstract	BK virus cystitis is known to occur following hematopoietic stem cell transplant (HSCT), but few cases exist in the literature following lung transplant. Because of the rarity of this presentation, patients may have missed diagnoses and prescribed ineffective treatments. We present our case of an atypical presentation of BK virus cystitis appearing as bladder carcinoma in situ in a lung transplant patient.
Language	English
Publishing date	2022-10-19
Publishing country	United States
Document type	Case Reports
ZDB-ID	2745459-9
ISSN	2214-4420
ISSN	2214-4420
DOI	10.1016/j.eucr.2022.102263
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