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Can p40 (Polyclonal) Replace p63 (Clone 4A4) in the Cytologic Diagnosis of Pulmonary Non-Small Cell Carcinoma?

Alexander, Melissa; Chiaffarano, Jeanine; Zhou, Fang; Cangiarella, Joan; Yee-Chang, Melissa; Simsir, Aylin
Objectives: Differentiating squamous cell carcinoma from adenocarcinoma (ACA) in cytology specimens can be challenging. Recent literature showed p40 had higher specificity than p63 for this purpose. Methods: We identified 190 cytology cases with p40 (polyclonal) and p63 (monoclonal clone 4A4) immunohistochemistry, including specimens from fine-needle aspirations (FNAs) and effusions. Results: ACAs of lung origin stained for p40 and p63 in 21% and 20% of cases, respectively, regardless of specimen site. Among lung FNAs of primary pulmonary ACAs (n = 42), 14% were positive for p40 and 24% were positive for p63. Of the 20 pulmonary ACAs in effusions, more cases showed p40 positivity (40%) compared with FNAs, whereas p63 were positive in 15%. Among metastatic ACAs from other sites (n = 14), more cases were positive for p40 than p63. Conclusions: Polyclonal p40 yields a level of false positivity in ACAs similar to p63, which is highest in effusions and is not limited to lung origin.
PMID: 28498881
ISSN: 1943-7722
CID: 2549272

Can noninvasive follicular thyroid neoplasm with papillary-like nuclear features be distinguished from classic papillary thyroid carcinoma and follicular adenomas by fine-needle aspiration?

Brandler, Tamar C; Zhou, Fang; Liu, Cheng Z; Cho, Margaret; Lau, Ryan P; Simsir, Aylin; Patel, Kepal N; Sun, Wei
BACKGROUND: Noninvasive encapsulated follicular variant of papillary thyroid carcinoma, a diagnosis implying malignancy as a variant of papillary thyroid carcinoma (PTC), has recently been reclassified to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on surgical pathology. Due to the effects of such a recategorization on rate of malignancy and clinical management algorithms, it is imperative that we explore whether presurgical fine-needle aspiration can differentiate NIFTP from PTC and follicular adenoma (FA). METHODS: Cytology slides from subjects with final surgical pathology resection diagnoses of NIFTP/encapsulated follicular variant of papillary thyroid carcinoma, classic PTC, and FA made between January 2013 and August 2016 were assessed. The Bethesda System diagnoses were tabulated and cytomorphologic features were analyzed for an association with surgical pathology diagnoses. RESULTS: A total of 56 NIFTP, 67 classic PTC, and 30 FA cases were included. The presurgical NIFTP diagnosis according to The Bethesda System was most often atypia of undetermined significance (37.5%) followed by suspicious for follicular neoplasm/follicular neoplasm (26.8%), suspicious for malignancy (17.9%), benign (10.7%), and positive for malignancy (7.1%). The most common NIFTP cytomorphologic features were nuclear enlargement (83.9%), nuclear crowding (82.1%), nuclear clearing (69.6%), and microfollicles (73.2%). All cytomorphologic features demonstrated statistically significant associations (P value range, <.001-.002) between NIFTP and PTC, whereas select cytomorphologic features demonstrated significant associations between NIFTP and FA. CONCLUSIONS: Several statistically significant associations appear to be present between cytomorphologic features and surgical diagnosis that may be used as clues to distinguish NIFTP, PTC, and FA on fine-needle aspiration. Although diagnostic confirmation of NIFTP must occur at the time of excision, similar to follicular neoplasms, the possibility of NIFTP may be raised preoperatively on cytology. Cancer Cytopathol 2017;125:378-88. (c) 2017 American Cancer Society.
PMID: 28296267
ISSN: 1097-0142
CID: 2593342

Can Noninvasive Follicular Thyroid Neoplasm with Papillary Like Nuclear Features (NIFTP) and Classical Papillary Thyroid Carcinoma (PTC) Be Distinguished by Fine Needle Aspiration (FNA)? [Meeting Abstract]

Brandler, Tamar C; Zhou, Fang; Cho, Margaret; Lau, Ryan P; Liu, Cheng; Simsir, Aylin; Patel, Kepal N; Sun, Wei
ISI:000393724400343
ISSN: 1530-0307
CID: 2506612

Impact of the Reclassification of Noninvasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma (EFVPTC) to Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) on the Current Management Guidelines of the Bethesda System for Reporting Thyroid Cytopathology [Meeting Abstract]

Lau, Ryan P; Paulsen, John D; Brandler, Tamar C; Simsir, Aylin; Zhou, Fang
ISI:000393724400397
ISSN: 1530-0307
CID: 2506632

Impact of the Reclassification of Noninvasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma (EFVPTC) to Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) on the Current Management Guidelines of the Bethesda System for Reporting Thyroid Cytopathology [Meeting Abstract]

Lau, Ryan P; Paulsen, John D; Brandler, Tamar C; Simsir, Aylin; Zhou, Fang
ISI:000394467300397
ISSN: 1530-0285
CID: 2517452

Can Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) and Classical Papillary Thyroid Carcinoma (PTC) Be Distinguished by Fine Needle Aspiration (FNA)? [Meeting Abstract]

Brandler, Tamar C; Zhou, Fang; Cho, Margaret; Lau, Ryan P; Liu, Cheng; Simsir, Aylin; Patel, Kepal N; Sun, Wei
ISI:000394467300343
ISSN: 1530-0285
CID: 2517432

"Low-grade squamous intraepithelial lesion, cannot exclude high-grade:" TBS says "Don't Use It!" should I really stop it?

Chiaffarano, Jeanine M; Alexander, Melissa; Rogers, Robert; Zhou, Fang; Cangiarella, Joan; Yee-Chang, Melissa; Elgert, Paul; Simsir, Aylin
BACKGROUND: The Bethesda System uses a two-tiered approach in the diagnosis of cervical squamous intraepithelial lesions (SILs). Occasionally, Papanicolaou (Pap) tests with evident low-grade SIL (LSIL) also have some features suggestive but not diagnostic of high-grade SIL (HSIL). This study reviews our experience with "Low-grade Squamous Intraepithelial Lesion, Cannot Exclude High-grade" (LSIL-H) and discusses the best approach to report such Paps if the LSIL-H interpretation is abandoned. METHODS: Abnormal Paps were identified between January and December 2014 that had surgical follow-up within 6 months. Their biopsy outcomes were compared. Statistical analysis was performed using Pearson's Chi-square and McNemar tests in SPSS software version 23. Statistical significance was defined as P
PMCID:5458421
PMID: 28603542
ISSN: 1742-6413
CID: 2593522

Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations

Zhou, Fang; Moreira, Andre L
CONTEXT: - In the burgeoning era of molecular genomics, immunoperoxidase (IPOX) testing grows increasingly relevant as an efficient and effective molecular screening tool. Patients with lung carcinoma may especially benefit from the use of IPOX because most lung carcinomas are inoperable at diagnosis and only diagnosed by small tissue biopsy or fine-needle sampling. When such small specimens are at times inadequate for molecular testing, positive IPOX results still provide actionable information. OBJECTIVE: - To describe the benefits and pitfalls of IPOX in the detection of biomarkers in lung carcinoma cytology specimens and small biopsies by summarizing the currently available commercial antibodies, preanalytic variables, and analytic considerations. DATA SOURCES: - PubMed. CONCLUSIONS: - Commercial antibodies exist for IPOX detection of aberrant protein expression due to EGFR L858R mutation, EGFR E746_A750 deletion, ALK rearrangement, ROS1 rearrangement, and BRAF V600E mutation, as well as PD-L1 expression in tumor cells. Automated IPOX protocols for ALK and PD-L1 detection were recently approved by the Food and Drug Administration as companion diagnostics for targeted therapies, but consistent interpretive criteria remain to be elucidated, and such protocols do not yet exist for other biomarkers. The inclusion of cytology specimens in clinical trials would expand patients' access to testing and treatment, yet there is a scarcity of clinical trial data regarding the application of IPOX to cytology, which can be attributed to trial designers' lack of familiarity with the advantages and limitations of cytology. The content of this review may be used to inform clinical trial design and advance IPOX validation studies.
PMID: 27588333
ISSN: 1543-2165
CID: 2352912

CEA in breast ductal secretions as a promising biomarker for the diagnosis of breast cancer: a systematic review and meta-analysis

Tang, Shifu; Zhou, Fang; Sun, Yifan; Wei, Lili; Zhu, Shengbo; Yang, Renqi; Huang, Yiyong; Yang, Jianqing
PURPOSE/OBJECTIVE:Other studies have shown that levels of carcinoembryonic antigen (CEA) in breast ductal secretions (BDS) differ significantly between breast cancer (BC) patients and healthy individuals, providing direct evidence for CEA in BDS as a promising biomarker for BC. This meta-analysis was designed to assess the potential diagnostic value of CEA in BDS. METHODS:Relevant articles were retrieved from Embase, Pubmed, and the Cochrane Library. Sensitivity, specificity, and diagnostic odds ratio (DOR) of CEA in BDS for diagnosing BC were pooled using random effects models. SROC and the area under the curve (AUC) were used to estimate overall diagnostic performance. RESULTS:This meta-analysis comprised five studies with a total of 340 BC patients and 448 healthy controls. For CEA in BDS, the pooled sensitivity, specificity, and DOR to diagnose BC were 58 % [95 % confidence interval (CI): 52-63 %], 87 % (95 % CI: 84-90 %), and 7.07 (95 % CI: 3.10-16.12), respectively. Moreover, the AUC of CEA in the diagnosis of BC was 0.8570. CONCLUSIONS:CEA in BDS is a promising biomarker in the diagnosis of BC and should be evaluated as a standard screening tool upon verification of our results in a larger study population.
PMID: 26898373
ISSN: 1880-4233
CID: 3215172

Low grade squamous intraepithelial Lesion, Cannot Exclude High Grade (LSIL-H): TBS says don't use it. Should i really stop it? [Meeting Abstract]

Chiaffarano, J; Alexander, M; Elgert, P A; Yee-Chang, M; Zhou, F; Simsir, A
Introduction: The Bethesda System (TBS) uses a two-tiered approach to cervical squamous intraepithelial lesions (SILs). Occasionally, Paps with evident low grade SIL (LSIL) also have some features suggestive but not diagnostic of high grade SIL (HSIL). These Paps in our and other institutions are reported as 'LSIL, Cannot Exclude HSIL' (LSIL-H). LSIL-H has been shown to represent an intermediate risk (between LSIL and HSIL) for harboring a high grade lesion/carcinoma (HGD+) on biopsy. However, TBS 2014 continues to discourage its use to prevent the re-emergence of a threetiered reporting system. We review our experience with LSIL-H and discuss the best approach to report such Paps if the LSIL-H category is abandoned. Materials and Methods: Abnormal Paps were identified between January and June 2014 which had surgical follow-up within six months. Their biopsy outcomes were compared. Statistical analysis was performed using the Fisher's exact test. Results: Table 1 summarizes surgical diagnoses for each abnormal Pap category (total n=571). The differences in detection rates of HGD+ between LSIL and LSIL-H Pap was significant (p=0.000), whereas between LSIL-H and 'Atypical squamous cells, cannot exclude HSIL' (ASC-H) was not (p=0.101). If the LSIL-Hcategory is abandoned and LSIL-Hcases are reported as ASC-H, the rate ofHGD+ for theASC-H categorywould decrease from 55% to 41% (p=0.3). Alternatively, if LSIL-H cases are downgraded to LSIL, the rate of HGD+ for the LSIL category would rise from 7% to 9% (p=0.27). Conclusions: The 'LSIL-H' category indeed detects more HGD+ than LSIL, and fewer HGD+ than ASC-H. If LSIL-H is eliminated, Paps with this finding are best reported as ASC-H to ensure that women with potential HGD+ undergo colposcopy in a timely manner. Reporting LSIL-H as LSIL may delay colposcopy since management of LSIL Pap depends on multiple factors (age, HPV status, etc). (Table Presented)
EMBASE:615337482
ISSN: 2213-2945
CID: 2620182