198 results on '"Lester J. Layfield"'
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2. Squamous Differentiation and Cytokeratin Expression in an Osteosarcoma: A Case Report and Review of the Literature
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Lester J. Layfield M.D., Lyska Emerson, Julia R. Crim, and Lor Randall
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Pathology ,RB1-214 - Abstract
Cytokeratin expression has been documented in a variety of sarcomas including synovial sarcomas, epithelioid sarcomas, Ewing's sarcomas and, rarely, osteosarcomas. In osteosarcomas immunohistochemically shown to expression cytokeratins, a component of epithelioid cells is generally present. These epithelioid cytokeratin positive cells raise the possibility of metastatic disease with prognostic and therapeutic implications differing from primary osteosarcoma. The cytokeratin-expressing cells of the cases reported in the literature have not shown definitive squamous differentiation with keratin pearl formation. We report a case of osteosarcoma in which islands of malignant squamous cells were present showing keratin pearl formation and expression of cytokeratins. more...
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- 2008
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3. Histopathologic Review of Previously Negative Prostatic Core Needle Biopsies following a New Diagnosis of Adenocarcinoma of the Prostate by Core Needle Biopsies: Implications for Quality Assurance Programs
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Jay Patel and Lester J. Layfield M.D.
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Pathology ,RB1-214 - Abstract
Programs for quality assurance are increasingly important in surgical pathology. Many quality assurance (QA) techniques for surgical pathology were adopted from procedures introduced in cytopathology. Surgical pathology specimens have diminished in size such that the majority of diagnostic biopsies of prostatic lesions are now core needle biopsies. These specimens raise issues similar to those of cytology specimens, including concerns regarding adequacy and the representative nature of the biopsy. Due to sample size, some neoplasms may not be diagnosed on initial biopsy, raising concerns regarding false negative results. Cytopathologists have instituted QA procedures including review of all previously negative slides received within five years prior to the new diagnosis of high grade squamous intraepithelial lesion or gynecologic malignancy. No such requirement exists in surgical pathology for review of core biopsies. The Department of Pathology at the University of Utah instituted a QA policy requiring review of prior negative prostatic needle biopsies following a new diagnosis of prostatic adenocarcinoma. We reviewed five years of QA records of prostate needle biopsy review. During this time, nine hundred and fifty-eight core biopsy sets were performed. Two hundred and ninety-five of these contained at least one biopsy with a diagnosis of adenocarcinoma. Two hundred and eight patients had a prior set of prostatic needle biopsies with a diagnosis of adenocarcinoma. The remaining 87 had prior biopsies with either a diagnosis of prostatic intraepithelial neoplasia (23), small atypical acinar proliferation (21) or no evidence of malignancy (43). QA review of these 87 cases revealed two biopsies which revealed foci of adenocarcinoma. Both had been initially diagnosed as no evidence of malignancy. The false negative rate for core biopsy was 0.68%. In an additional twenty-one cases, microscopic foci of atypical small acinar proliferations were found in core biopsies antedating the positive core biopsy (7.1%). more...
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- 2008
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4. Limited usefulness of classic MR findings in the diagnosis of tenosynovial giant cell tumor
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Lester J. Layfield, James Derek Stensby, Andrea Evenski, Julia R. Crim, and Samantha L Dyroff
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Pathology ,medicine.medical_specialty ,business.industry ,Xanthoma ,medicine.disease ,Lesion ,Tendon sheath ,medicine.anatomical_structure ,Pigmented villonodular synovitis ,Hemosiderin ,medicine ,Radiology, Nuclear Medicine and imaging ,Giant Cell Tumors ,Differential diagnosis ,medicine.symptom ,business ,Subcutaneous tissue - Abstract
To determine the frequency with which MRI of tenosynovial giant cell tumor demonstrates hemosiderin, visible intralesional fat signal, and proximity to synovial tissue. This is a retrospective study of 31 cases of tenosynovial giant cell tumors which had concomitant MRI. Images were examined for lesion size, morphology, origin, bone erosions, MRI signal characteristics, contrast enhancement, and blooming artifact, comparing prospective and retrospective reports. Histology was reviewed for the presence of hemosiderin and xanthoma cells. Eight lesions were diffuse and 23 were localized nodules. Three lesions were located in subcutaneous tissue and 4 adjacent to tendons beyond the extent of their tendon sheath. All lesions exhibited areas of low T1- and T2-weighted signal. Blooming artifact on gradient echo imaging was present in 86% of diffuse and only 27% of nodular disease. There was interobserver variability of 40% in assessing blooming. Iron was visible on H&E or iron stain in 97% of cases. Fat signal intensity was seen in only 3% of cases, although xanthoma cells were present on in 48%. The correct diagnosis was included in the prospective radiology differential diagnosis in 86% of diffuse cases and 62% of nodular cases. Blooming on GRE MRI has low sensitivity for nodular tenosynovial giant cell tumors and is not universal in diffuse tumors. There was high interobserver variability in assessment of blooming. Intralesional fat signal is not a useful sign and may occur adjacent to tendons which lack a tendon sheath and may occur in a subcutaneous location. more...
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- 2021
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5. Cytologic features of sebaceous, lymphadenoma, and sebaceous lymphadenocarcinoma: Differential diagnostic considerations
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Lester J. Layfield, Maryna Vazmitsel, and Magda Esebua
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Pathology ,medicine.medical_specialty ,Histology ,Sebaceous lymphadenoma ,Population ,030209 endocrinology & metabolism ,Adenocarcinoma ,Pathology and Forensic Medicine ,Sebaceous adenoma ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,education ,education.field_of_study ,medicine.diagnostic_test ,Salivary gland ,business.industry ,General Medicine ,Adenolymphoma ,Salivary Gland Neoplasms ,medicine.disease ,Parotid gland ,Fine-needle aspiration ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Differential diagnosis ,business - Abstract
BACKGROUND Sebaceous lymphadenomas and sebaceous lymphadenocarcinomas are uncommon neoplasms occurring predominately within the parotid gland. Cytomorphology of these neoplasms is rarely reported. Occasional reports have discussed the cytomorphological features of these neoplasms but criteria distinguishing sebaceous lymphadenomas from lymphadenocarcinomas have not been described. METHODS The senior authors' consultation files and records of the University of Missouri were searched for all cases with a diagnosis of sebaceous adenoma, lymphadenoma, lymphadenocarcinoma, and adenocarcinoma. Slides from these cases were reviewed by the authors for cytologic features characteristic of these neoplasms. These features were compared with other salivary gland lesions in the differential diagnosis and for utility in separating benign from malignant sebaceous neoplasms. RESULTS Three sebaceous lymphadenomas and one sebaceous lymphadenocarcinoma were found. Smears contained large numbers of mature lymphocytes dispersed in a watery or bloody background. Scattered among the lymphoid cells were small nests of epithelial cells characterized by a finely to coarsely vacuolated cytoplasm. The majority of cells contained bland nuclei with finely granular chromatin and conspicuous nucleoli. A second population of small basaloid cells was present. The single sebaceous lymphadenocarcinoma had a similar cytomorphology. CONCLUSIONS Sebaceous lymphadenomas can be distinguished from other neoplasms within the differential diagnosis due to their prominent lymphoid background and population of epithelial cells with a finely to coarsely vacuolated cytoplasm. The nuclei are bland but have conspicuous nucleoli. Based on our small series, cytomorphologic features are inadequate to definitively separate sebaceous lymphadenomas from lymphadenocarcinomas. more...
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- 2020
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6. Soft tissue tumor diagnosis: A three prong approach utilizing pattern analysis, immunocytochemistry, and molecular diagnostics
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Lester J. Layfield
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Pathology ,medicine.medical_specialty ,Histology ,Soft Tissue Neoplasm ,Cytodiagnosis ,Immunocytochemistry ,Soft Tissue Neoplasms ,030209 endocrinology & metabolism ,Pathology and Forensic Medicine ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Biopsy ,Humans ,Medicine ,Pathology, Molecular ,Medical diagnosis ,medicine.diagnostic_test ,business.industry ,Soft tissue ,General Medicine ,Molecular diagnostics ,Immunohistochemistry ,Fine-needle aspiration ,030220 oncology & carcinogenesis ,business - Abstract
Tissue diagnosis of a soft tissue neoplasm is of paramount importance for the development of an appropriate treatment plan. Biopsy technique including approach and biopsy method is important to the success of diagnosis and subsequent treatment. Histologic and cytologic diagnoses are difficult and complicated by the large number of soft tissue lesions described, distinctly different biopotential for morphologically similar lesions, often small biopsy specimen size, and the generally limited experience many pathologists have in the diagnosis of soft tissue neoplasms. While utilized less frequently than core-needle biopsies, fine-needle aspiration is a valuable initial approach for the classification of soft tissue neoplasms. The combination of pattern based morphologic analysis, immunohistochemistry, and molecular diagnostics represents a utilitarian and generally successful approach for the diagnosis of soft tissue lesions. more...
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- 2019
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7. PD-L1 expression in sarcomas: An immunohistochemical study and review of the literature
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Christopher R Cunningham, Lester J. Layfield, Leslie G. Dodd, and Magda Esebua
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Pathology ,medicine.medical_specialty ,biology ,business.industry ,medicine.medical_treatment ,Clone (cell biology) ,Sarcoma ,General Medicine ,Immunotherapy ,medicine.disease ,Immunohistochemistry ,B7-H1 Antigen ,Pathology and Forensic Medicine ,Antineoplastic Agents, Immunological ,PD-L1 ,medicine ,biology.protein ,Pd l1 expression ,Programmed death 1 ,Antibody ,business ,Retrospective Studies - Abstract
Background Immunotherapy is increasingly used for treatment of metastatic melanoma and carcinomas. PD-1 (programmed death 1) and its associated ligand (PD-L1) inhibits the activation of T-lymphocytes. This inhibition can be impacted by a number of drugs. Response to these drugs is predicted by assessment of PD-L1 expression. PD-L1 expression varies between 19% and 92% in melanomas and carcinomas. PD-L1 expression is less well documented for sarcomas. Design Fifty-six sarcomas of various histopathologic types were immunohistochemically stained (IHC) for PD-L1 using the antibody clone SP263 (Ventana, Tuscan, AZ). Membrane staining of tumor cells was quantitated as a percentage of total tumor cells. Sarcomas were judged as non-expressors (less than 1%) low-expressors (1 to 50%) and high expressors (greater than 50%). The percentage of each type of sarcoma judged as an expressor was determined. Results Table 1 documents the percentage of each type of sarcoma expressing PD-L1. 14% of sarcomas expressed PD-L1. Percentage of sarcomas expressing PD-L1 varied significantly between types but the majority of sarcomas were non-expressors. Conclusion PD-L1 IHC expression is valuable in predicting response to immune-modulating drugs. Such therapies may be useful for treatment of metastatic sarcomas. Expression of PD-L1 in carcinomas and melanomas is variable ranging from 19% to 92%. In our study, a minority (14%) of sarcomas expressed PD-L1. Other studies have shown similar results with between 1.4 and 59% (average 24%) of sarcomas expressing PD-L1. Expression appears to be sarcoma type specific. These finding suggest that PD-L1 based therapy may be less useful in sarcomas than in other malignancies. more...
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- 2021
8. Myxoid neoplasms of bone and soft tissue: a pattern-based approach
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Leslie G. Dodd, Jerzy Klijanienko, and Lester J. Layfield
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Fibrosarcoma ,Biopsy, Fine-Needle ,Chondrosarcoma ,Pattern analysis ,030209 endocrinology & metabolism ,Diagnostic accuracy ,Bone Neoplasms ,Soft Tissue Neoplasms ,Pathology and Forensic Medicine ,Diagnosis, Differential ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,medicine ,Humans ,Nuclear atypia ,Aged ,Ganglion Cysts ,medicine.diagnostic_test ,business.industry ,Soft tissue ,Middle Aged ,Liposarcoma, Myxoid ,Fine-needle aspiration ,030220 oncology & carcinogenesis ,Female ,business ,Myxoma - Abstract
Introduction The accurate diagnosis of musculoskeletal neoplasms is difficult but a pattern-based approach combined with ancillary testing has been shown to improve diagnostic accuracy. The pattern-based approach is particularly appropriate for myxoid lesions. Materials and methods The authors reviewed their personal experience of over 3 decades of diagnosing myxoid neoplasms of musculoskeletal lesions. Results The authors found that myxoid lesions can be accurately classified based on cell type, nuclear atypia, presence of blood vessel fragments, as well as the results of immunohistochemical and molecular testing. Conclusions Musculoskeletal lesions with a prominence of myxoid or chondroid material in the background can be accurately diagnosed using pattern analysis and ancillary testing. more...
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- 2020
9. Cell block cellularity: A comparison of two fixatives and their impact on cellularity
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Lester J. Layfield, Nitya Prabhakaran, Magda Esebua, Harijyot S. Sohal, Richard D. Hammer, Jonathan Ross Ang, Robert L. Schmidt, and Mohammed Alnijoumi
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Pathology ,medicine.medical_specialty ,Tissue Fixation ,Histology ,business.industry ,Biopsy ,030209 endocrinology & metabolism ,General Medicine ,Pathology and Forensic Medicine ,Fixatives ,03 medical and health sciences ,0302 clinical medicine ,Formaldehyde ,Neoplasms ,030220 oncology & carcinogenesis ,medicine ,Humans ,business ,Cell block ,Fixative ,Fixation (histology) - Abstract
Background Ancillary testing including immunohistochemistry and molecular diagnostics has become an increasingly important component for the evaluation of cytologic specimens. Ancillary testing is important not only for diagnosis but also for predictive and prognostic evaluation. While a number of substrates are appropriate for ancillary testing, cell block specimens are commonly utilized and the success of ancillary testing depends on cell-block cellularity. Methods Forty-six pairs of cases each fixed in both formalin and CytoLyt were each analyzed by two evaluators for overall cellularity. Linear regression was used to assess inter-rater reliability of cell counts for each method. Cellularity scores for each case were obtained by averaging the scores for each rater and cellularity was compared between the methods. Results Inter-rater agreement was very good for both methods. The coefficient of determination was 1.0 and 0.99 for the CytoLyt and formalin methods respectively. Cell blocks using the CytoLyt method have lower levels of cellularity than cell blocks performed by the formalin method. Conclusions Cell blocks prepared using a formalin fixative yield significantly greater cellularity than those produced by the CytoLyt method. Formalin fixation appears to optimize cellularity of cell blocks useful for ancillary testing. more...
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- 2018
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10. Solitary fibrous tumors: Clinical and imaging features from head to toe
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Akram M. Shaaban, Julia R. Crim, Mohamed Badawy, Ayman Nada, Ayman H. Gaballah, Khalid Kabeel, Lester J. Layfield, and Khaled M. Elsayes
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Surgical resection ,Solitary fibrous tumor ,Pathology ,medicine.medical_specialty ,business.industry ,General Medicine ,Toes ,medicine.disease ,World health ,Diagnosis, Differential ,Anatomical sites ,Solitary Fibrous Tumors ,medicine ,Humans ,Immunohistochemistry ,Radiology, Nuclear Medicine and imaging ,business - Abstract
Solitary fibrous tumors (SFTs) are rare fibroblastic mesenchymal tumors that are usually benign with variable malignant potential. They can develop in any organ due to their spindle cell origin. The exact etiology of solitary fibrous tumors is unknown. The majority of SFTs are benign with 10% to 30% of them exhibiting aggressive and malignant features. The aggressiveness of this type of tumor is not associated with its histological features, which makes surgical resection the treatment of choice. We will review the clinical and radiological features and possible differential diagnoses of SFTs according to their anatomical sites following the World Health Organization 2020 classification. more...
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- 2022
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11. Mast cell infiltration and activation in the gallbladder wall: Implications for the pathogenesis of functional gallbladder disorder in adult patients
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Juwairiya Arshi, Magda Esebua, and Lester J. Layfield
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Colic ,medicine.medical_treatment ,Gallbladder disease ,Biliary dyskinesia ,Gallbladder Diseases ,Pathology and Forensic Medicine ,Young Adult ,Humans ,Medicine ,Cholecystectomy ,Mast Cells ,Ultrasonography ,medicine.diagnostic_test ,business.industry ,Gallbladder ,Degranulation ,Gallbladder Disorder ,General Medicine ,Middle Aged ,medicine.disease ,Mast cell ,medicine.anatomical_structure ,Cholescintigraphy ,Female ,business - Abstract
Background Functional gallbladder disorder (FGD) is characterized by recurrent biliary colic with a decreased gallbladder ejection fraction on cholescintigraphy but absence of visible gallbladder abnormalities on ultrasonography. FGD is generally regarded as a primary gallbladder motility disturbance, however, the underlying pathophysiology remains largely unknown. In this study, we investigated the potential role of mast cells in the pathogenesis of FGD by examining mast cell density and activation in the gallbladder wall. Design Twenty adult patients with FGD undergoing cholecystectomy were included in the study. Seven patients with no gallbladder disease were served as controls who were subject to incidental cholecystectomy during abdominal surgery such as partial hepatectomy. The density of mast cells in the gallbladder wall was assessed by immunohistochemistry and by toluidine blue special stain. Mast cell activation was evaluated by calculating the percentage of degranulated mast cells on toluidine blue stain. Results Compared to the controls, patients with FGD showed a significant increase in mast cell infiltration in the gallbladder walls. Peak mast cell accumulation was predominantly located in the inner muscular layer of the gallbladder wall. Mast cell activation was also markedly increased in the FGD group as evidenced by significantly enhanced mast cell degranulation. Conclusions Mast cell infiltration and activation were significantly increased in the muscular wall of gallbladders from FGD patients, suggesting potential involvement of mast cells in the compromised gallbladder motility in adult patients with FGD. more...
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- 2021
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12. Reporting of fine needle aspiration (FNA) specimens of salivary gland lesions: A comprehensive review
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Virginia A. LiVolsi, Kathleen T. Montone, Shuanzeng Wei, Lester J. Layfield, and Zubair W. Baloch
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Pathology ,medicine.medical_specialty ,Histology ,Risk of malignancy ,Biopsy, Fine-Needle ,education ,030209 endocrinology & metabolism ,Classification scheme ,Medical Records ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Salivary gland.FNA ,Cytology ,medicine ,Humans ,medicine.diagnostic_test ,Salivary gland ,business.industry ,General Medicine ,Salivary Gland Neoplasms ,Fine-needle aspiration ,medicine.anatomical_structure ,Cytopathology ,030220 oncology & carcinogenesis ,Salivary gland neoplasm ,Radiology ,business - Abstract
Currently, there is no uniform classification scheme available for reporting of salivary gland fine-needle aspiration (FNA) specimens. Recently, an International group of pathologists has recommended a tiered classification scheme for reporting of salivary gland FNA results known as the "Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)." We performed a comprehensive review of the published literature on FNA of salivary gland lesions by employing the diagnostic categories of the MSRSGC to evaluate their reliability in the management of salivary gland lesions. A comprehensive review of the literature was carried out through PubMed from 1987 to 2015 to identify studies which categorized the cytologic diagnoses and included surgical follow-up. Only cases with histopathologic follow-up were included in the analysis. Twenty-nine studies comprising 4514 cases of salivary gland FNAs with surgical follow-up were included in this study. The cytologic diagnoses were categorized into the following categories proposed by MSRSGC. The number of cases in each diagnostic category and the risk of malignancy (ROM) were as follows: Non-Diagnostic-100 cases (ROM- 25.0% ± 16.7%), Non-Neoplastic-587 cases (ROM: 10.2% ± 5.5%), Benign Neoplasm -2673 cases (ROM: 3.4% ± 1.3%), Salivary Gland Neoplasm of Undetermined Malignant Potential (SUMP)-64 cases(ROM: 37.5% ± 24.7%), Suspicious for Malignant neoplasm-70 cases(ROM: 58.6% ± 19.5%), and Malignant-1012 cases(ROM: 91.9% ± 3.5%). A tiered classification scheme as proposed by MSRSGC may prove helpful in effectively guiding clinical management of patients with salivary gland lesions. more...
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- 2017
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13. Quality assurance of anatomic pathology diagnoses: Comparison of alternate approaches
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Lester J. Layfield and Shellaine R. Frazier
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030213 general clinical medicine ,medicine.medical_specialty ,Pathology ,Quality Assurance, Health Care ,Pathology, Surgical ,business.industry ,Anatomical pathology ,Cell Biology ,Patient care ,Pathology and Forensic Medicine ,Surgical pathology ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Expert opinion ,medicine ,Humans ,Medical physics ,Dermatopathology ,Diagnostic Errors ,Medical diagnosis ,Detection rate ,business ,Quality assurance - Abstract
Objectives Traditionally, a 10% review has been the basis for quality assurance programs in anatomic pathology. The effectiveness of such reviews has been questioned and alternative methodologies suggested. The study investigates the error detection rates for four quality assurance protocols. Methods The detection rate for diagnostic errors in surgical pathology was calculated over a one year period using four different review procedures comprising: random 10% review, correlation of internal and external diagnoses following solicited external expert opinion, correlation of internal diagnoses with outside diagnoses in cases sent for review at a second institution treating the patient along with a focused review of dermatopathology cases over a 3 month period. Error rate was expressed as percentage of reviewed cases where the initial diagnosis differed from the review diagnosis. Error rates detected by each method were compared among the methods Results The 10% random review detected seventeen errors in 2147 cases (0.8%). Solicited case consultations requested by clinicians or internal pathologists detected five diagnostic errors in seventy cases (7.1%). Unsolicited reviews by outside institutions in the course of patient care detected three diagnostic errors in 190 cases (1.6%). Review of the dermatopathology material disclosed 5 diagnostic errors in 59 cases (8.5%). Conclusions Focused reviews initiated by diagnostic concerns of a clinician or pathologist, unsolicited reviews because of treatment at another institution and sub-specialty based reviews appear to be more effective in detecting diagnostic errors than the 10% random review. Quality assurance programs should include focused reviews in addition to 10% random review to maximize error detection. more...
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- 2017
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14. Afirma Testing in Thyroid Nodules with Indeterminate Cytology: A single Medical Institute Experience
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Tao Zhang, Magda Esebua, Z Yang, and Lester J. Layfield
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Thyroid nodules ,Thyroid Gland Follicular Adenoma ,Pathology ,medicine.medical_specialty ,business.industry ,Thyroid ,General Medicine ,medicine.disease ,Hurthle Cell Tumor ,medicine.anatomical_structure ,Cytology ,medicine ,Molecular diagnostic techniques ,Indeterminate ,business - Abstract
Introduction/Objective About 10 to 30% of thyroid fine needle aspiration (FNA) nodules have indeterminate cytology, including Bethesda III, IV, and V. Afirma Gene Expression Classifier (GEC) measuring the expression of 167 mRNA was designed to classify the indeterminate thyroid nodules into benign and suspicious categories. This study aimed to evaluate the clinical performance of the Afirma GEC testing in these indeterminate thyroid lesions. Methods Medical records of patients with indeterminate thyroid FNA results and corresponding Afirma GEC results from November 2012 to December 2019 were retrieved. Subsequent surgical follow-up results were obtained. GEC results were compared to the histologic diagnoses. Results 1. There were 77 cases with indeterminate thyroid FNA results. Cytology diagnosis included 67 Bethesda III and 10 Bethesda IV. Afirma GEC results were benign for 41 cases (53%), suspicious for 32 cases (42%), and non- diagnostic for 4 cases (5%). Twenty seven of 32 cases (84%) with suspicious GEC results had surgical follow-up which revealed 12 malignant and 15 benign histologic diagnoses. Only 11 of 41 cases (27%) with benign GEC results had surgery which showed 8 benign and 3 malignant diagnoses. Based on the data, the sensitivity of this test is 80% and specificity is 65%. Positive predictive value (PPV) is 44% and negative predictive value (NPV) is 73%. The false positive cases include 5 Hurthle cell adenoma, 4 nodular hyperplasia, 3 follicular adenoma, 2 Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFPT), and 1 lymphocytic thyroiditis. The false negative cases include 2 minimally invasive follicular carcinoma (from same patient) and 1 papillary thyroid carcinoma. Conclusion 1. We demonstrated in this study that a little more than half of the cases with indeterminate thyroid cytology had negative Afirma GEC results. 2.Afirma test has relatively low specificity (65%) and PPV (44%). The sensitivity (80%) and NPV (73%) is relatively higher but is lower than the values in most literature. This could be due to the fact that majority of the Afirma GEC negative cases in this study did not have surgical follow-up and the sample size is small. 3.Afirma GEC test is a relatively good “rule-out” molecular test for indeterminate thyroid nodules but is not a reliable “rule-in” test due to the low specificity and PPV. more...
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- 2020
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15. Accuracy and Reproducibility of Nuclear/Cytoplasmic Ratio Assessments in Urinary Cytology Specimens
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Magda Esebua, Richard D. Hammer, Van Nguyen, Shellaine R. Frazier, William W. Bivin, Ilker Ersoy, Robert L. Schmidt, and Lester J. Layfield
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Accuracy and precision ,Pathology ,medicine.medical_specialty ,Reproducibility ,Histology ,business.industry ,Coefficient of variation ,Urinary system ,030209 endocrinology & metabolism ,General Medicine ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Cytology ,Medicine ,Critical range ,Statistical analysis ,business ,Nuclear medicine ,Kappa - Abstract
Background Evaluation of the nuclear to cytoplasmic ratio is commonly used for assessment of the presence of malignancy and for grading and typing of malignant neoplasms. Despite its widespread usage, little information exists regarding the accuracy and reproducibility of non-automated assessment. Methods Forty-seven cells obtained from Papanicolaou stained urine cytologies were assessed by quantitative image analysis for nuclear area and cell area. The nuclear/cytoplasmic ratio was calculated. Visual estimates of the N/C ratio were made by six pathologists. Statistical analysis was performed to determine accuracy, precision, and interrater reliability. Results True N/C ratios varied from 0.02 to 0.81. 27% of cases demonstrated a true N/C ratio between 0.5 and 0.7. Quantitative estimates of N/C ratios were less precise and less accurate at high N/C ratios. The coefficient of variation was 27%. The majority of raters demonstrated decreased accuracy and precision of estimates as N/C ratio increased. Overall classification accuracy was 73%. Accuracy of classification was 53% for cases with a true N/C ratio between 0.4 and 0.8. Absolute interrater agreement was 75%. Chance corrected agreement (kappa) was 0.54. Conclusions Visual quantitation of N/C ratio showed only a fair correlation with actual N/C ratio with correlation decreasing with increasing N/C ratio. In the critical range, 0.5–0.7 N/C ratio both interobserver correlation and correlation with true N/C ratio may be insufficiently accurate for precise category assignment as used in the Paris System. Diagn. Cytopathol. 2017;45:107–112. © 2016 Wiley Periodicals, Inc. more...
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- 2017
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16. Cytologic separation of branchial cleft cyst from metastatic cystic squamous cell carcinoma: A multivariate analysis of nineteen cytomorphologic features
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Lester J. Layfield, Magda Esebua, and Robert L. Schmidt
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Frozen section procedure ,Pathology ,medicine.medical_specialty ,Histology ,medicine.diagnostic_test ,business.industry ,Branchial Cyst ,General Medicine ,medicine.disease ,Pathology and Forensic Medicine ,Squamous carcinoma ,03 medical and health sciences ,0302 clinical medicine ,Fine-needle aspiration ,030220 oncology & carcinogenesis ,Cytology ,Pharyngeal groove ,Carcinoma ,medicine ,Branchial cleft cyst ,030223 otorhinolaryngology ,business - Abstract
Background The separation of branchial cleft cysts from metastatic cystic squamous cell carcinomas in adults can be clinically and cytologically challenging. Diagnostic accuracy for separation is reported to be as low as 75% prompting some authors to recommend frozen section evaluation of suspected branchial cleft cysts before resection. We evaluated 19 cytologic features to determine which were useful in this distinction. Methods Thirty-three cases (21 squamous carcinoma and 12 branchial cysts) of histologically confirmed cystic lesions of the lateral neck were graded for the presence or absence of 19 cytologic features by two cytopathologists. The cytologic features were analyzed for agreement between observers and underwent multivariate analysis for correlation with the diagnosis of carcinoma. Results Interobserver agreement was greatest for increased nuclear/cytoplasmic (N/C) ratio, pyknotic nuclei, and irregular nuclear membranes. Recursive partitioning analysis showed increased N/C ratio, small clusters of cells, and irregular nuclear membranes were the best discriminators. Conclusion The distinction of branchial cleft cysts from cystic squamous cell carcinoma is cytologically difficult. Both digital image analysis and p16 testing have been suggested as aids in this separation, but analysis of cytologic features remains the main method for diagnosis. In an analysis of 19 cytologic features, we found that high nuclear cytoplasmic ratio, irregular nuclear membranes, and small cell clusters were most helpful in their distinction. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc. more...
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- 2016
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17. Cell-blocks and immunohistochemistry
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Vinod B. Shidham and Lester J. Layfield
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Pathology ,medicine.medical_specialty ,medicine.drug_class ,Review Article ,Monoclonal antibody ,Pathology and Forensic Medicine ,Surgical pathology ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,CMAS ,Cellblock ,medicine ,Multiplex ,SCIP approach ,Cell block ,Shidham method ,Fixation (histology) ,Monograph ,Subtractive coordinate immunoreactivity pattern ,business.industry ,030224 pathology ,Immunohistochemistry ,Standard optimum cell-block protocol ,030220 oncology & carcinogenesis ,SOCP NextGen CelBloking ,business ,Cell-block ,Immunostaining ,IHC - Abstract
The interpretation of results on immunostained cell-block sections has to be compared with the cumulative published data derived predominantly from formalin-fixed paraffin-embedded (FFPE) tissue sections. Because of this, it is important to recognize that the fixation and processing protocol should not be different from the routinely processed FFPE surgical pathology tissue. Exposure to non-formalin fixatives or reagents may interfere with the diagnostic immunoreactivity pattern. The immunoprofile observed on such cell-blocks, which are not processed in a manner similar to the surgical pathology specimens, may not be representative resulting in aberrant results. The field of immunohistochemistry (IHC) is advancing continuously with the standardization of many immunomarkers. A variety of technical advances such as multiplex IHC with refined methodologies and automation is increasing its role in clinical applications. The recent addition of rabbit monoclonal antibodies has further improved sensitivity. As compared to the mouse monoclonal antibodies, the rabbit monoclonal antibodies have 10 to 100 fold higher antigen affinity. Most of the scenarios involve the evaluation of coordinate immunostaining patterns in cell-blocks with relatively scant diagnostic material without proper orientation which is usually retained in most of the surgical pathology specimens. These challenges are addressed if cell-blocks are prepared with some dedicated methodologies such as NextGen CelBloking™ (NGCB) kits. Cell-blocks prepared by NGCB kits also facilitate the easy application of the SCIP (subtractive coordinate immunoreactivity pattern) approach for proper evaluation of coordinate immunoreactivity. Various cell-block and IHC-related issues are discussed in detail. more...
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- 2021
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18. Mandibular Invasion by Oral Squamous Cell Carcinoma: Clinicopathologic Features of 74 Cases
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Lester J. Layfield, Robert P. Zitsch, Arya W. Namin, Jumah Ahmad, and Jeffrey B. Jorgensen
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Osteoclasts ,Cell Count ,03 medical and health sciences ,0302 clinical medicine ,Osteoclast ,medicine ,Humans ,Basal cell ,Neoplasm Invasiveness ,030223 otorhinolaryngology ,Head and neck ,Aged ,Retrospective Studies ,Aged, 80 and over ,Osteoblasts ,business.industry ,Prior Radiation ,Mandible ,Fibroblasts ,Middle Aged ,Survival Rate ,Mandibular Neoplasms ,medicine.anatomical_structure ,Treatment Outcome ,Otorhinolaryngology ,Depth of invasion ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Surgery ,Female ,Mouth Neoplasms ,business - Abstract
(1) For patients with oral squamous cell carcinoma (OSCC) and mandibular invasion, to determine whether prior radiation to the head and neck region (PXRTHN) affects the density of osteoblasts, osteoclasts, or fibroblasts along the tumor interface invading the mandible and whether this is significantly associated with overall survival. (2) To identify clinicopathologic features that are associated with overall survival.Case series with chart review.University of Missouri hospital.Retrospective review of 74 cases with pathologically confirmed mandible invasion by OSCC and surgical treatment between January 1, 2005, and December 31, 2015. A board-certified anatomic pathologist reviewed the slides from all mandibulectomy cases.The mean density of osteoclasts was 2.0 per linear mm among the patients with PXRTHN and 7.1 among those without PXRTHN ( P.001). Positive soft tissue frozen section margin was significantly associated with overall survival on univariate analysis ( P.001; hazard ratio [HR], 0.34; 95% CI, 0.19-0.62) and multivariate analysis ( P = .026; HR, 0.41; 95% CI, 0.19-0.90). Maximum tumor dimension was significantly associated with overall survival on univariate analysis ( P = .021; HR, 1.19; 95% CI, 1.03-1.38) and multivariate analysis ( P = .002; HR, 1.49; 95% CI, 1.16-1.93). Osteoclast, osteoblast, and fibroblast density were not associated with overall survival.(1) Osteoclast density along the tumor front is significantly lower among patients with PXRTHN. Stromal cell density was not associated with overall survival. (2) Positive soft tissue frozen section margin and maximum tumor dimension are significantly associated with overall survival among patients with mandibular invasion by OSCC. more...
- Published
- 2019
19. The Application of The Milan System Salivary Gland Tumor Fine-Needle Aspiration Cytology
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Maryna Vazmitsel, Magda Esebua, and Lester J. Layfield
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Pathology ,medicine.medical_specialty ,Salivary gland tumor ,business.industry ,Fine needle aspiration cytology ,medicine ,business ,Pathology and Forensic Medicine - Published
- 2019
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20. Histomorphologic Features of Biopsy Sites Following Excisional and Core Needle Biopsies of the Breast
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Lester J. Layfield, Elizabeth Schanzmeyer, and Shellaine R. Frazier
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Breast biopsy ,Pathology ,medicine.medical_specialty ,Breast Neoplasms ,Malignancy ,Diagnosis, Differential ,Stereotaxic Techniques ,Breast Diseases ,Biopsy Site ,Predictive Value of Tests ,Biopsy ,Internal Medicine ,medicine ,Carcinoma ,Humans ,Fat necrosis ,Fibrocystic Breast Disease ,Hyperplasia ,medicine.diagnostic_test ,business.industry ,Biopsy, Needle ,Granulation tissue ,Prognosis ,medicine.disease ,Squamous metaplasia ,medicine.anatomical_structure ,Oncology ,Female ,Surgery ,business ,Precancerous Conditions - Abstract
Mammographic studies have documented a number of architectural changes occurring around breast biopsy sites. These changes are well described in the radiological literature, but similar studies do not appear to be present in the pathology literature. We reviewed 100 consecutive mastectomy specimens from women who had undergone prior core needle or excisional biopsies. Multiple sections of the needle tract or excisional biopsy site were reviewed and morphologic findings reported. Hemorrhage, fat necrosis, granulation tissue, necrosis of fibrous tissue, and epithelium along with fibrosis and foreign body type giant cells were common features. Less frequent were areas of synovial metaplasia, atypical spindle cells, atypical duct-like structures, single atypical cells, squamous metaplasia, proliferations of abnormal blood vessels, and hemosiderin deposition. The misinterpretation of atypical spindle cells, single atypical cells, atypical duct-like structures and squamous metaplasia could result in the false-positive diagnosis of residual malignancy. Careful attention to the reactive nature of these changes aids in their distinction from carcinoma. more...
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- 2015
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21. Is It Time for a New Gold Standard? FISH vs Cytogenetics in AML DiagnosisThe Authors’ Reply
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Richard D. Hammer, Mark R. Litzow, Curtis A. Hanson, Rong He, Daniel L. Van Dyke, Paul J. Kurtin, Anne E. Wiktor, Donald C. Doll, Rhett P. Ketterling, Lester J. Layfield, Kaaren K. Reichard, and Matthew T. Howard more...
- Subjects
Response rate (survey) ,Pathology ,medicine.medical_specialty ,Pediatrics ,Conventional cytogenetics ,Myeloid ,medicine.diagnostic_test ,business.industry ,Cytogenetics ,General Medicine ,Gold standard (test) ,Turnaround time ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,medicine ,%22">Fish ,business ,030215 immunology ,Fluorescence in situ hybridization - Abstract
We read with interest the recent article by He et al1 comparing conventional karyotyping and fluorescence in situ hybridization (FISH) in acute myeloid leukemia (AML). While the authors clearly show no advantage to FISH when karyotyping is adequate and propose an algorithmic approach to testing, there is no discussion regarding practical matters, such as turnaround time, potential delay in diagnosis, and actual cost vs benefit. Cytogenetics and FISH are often send-out tests at many institutions, and as noted, this is often done concurrently rather than sequentially. Chromosome analysis has long been the gold standard for identification of the common, recurrent chromosome abnormalities in AML. However, this analysis requires dividing cells, takes 5 to 7 days to process, and can miss subtle or cryptic rearrangements (eg, inv[16] and MLL anomalies). We, like others, are also looking at best practices to provide value and quality care in the new health care environment. We find the algorithmic strategy is beneficial in many situations and can prevent unnecessary testing. Being curious of the implications in this scenario, we asked for a turnaround time report for conventional cytogenetics and multiprobe AML FISH panel from our reference laboratory (a large national reference laboratory) for the past 6 months. The average turnaround time for cytogenetics was 7 days vs 2.5 days for FISH. This could potentially result in a significant delay of definitive treatment regimens or increased length of stay. In this regard, time from diagnosis to treatment (TDT) has been reported to predict survival in younger but not older patients with AML.2 In that study, response rate and survival were decreased after a 5-day treatment delay in patients younger than 60 years. On the other hand, Bertoli et al3 recently reported that TDT did not adversely affect outcome of patients with AML. Nonetheless, … more...
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- 2016
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22. The Papanicoloau Society of Cytopathology Guidelines for the Classification of Pancreaticobiliary Lesions
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Lester J. Layfield
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Pathology ,medicine.medical_specialty ,Cytopathology ,business.industry ,General surgery ,Medicine ,business ,Pathology and Forensic Medicine - Published
- 2015
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23. Metastatic Tumors, Lymphomas, and Rare Tumors of the Thyroid
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Kennichi Kakudo and Lester J. Layfield
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0301 basic medicine ,endocrine system ,Pathology ,medicine.medical_specialty ,endocrine system diseases ,medicine.diagnostic_test ,business.industry ,Thyroid ,medicine.disease ,Malignancy ,Primary Neoplasm ,Lymphoma ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Fine-needle aspiration ,medicine.anatomical_structure ,Paraganglioma ,Mucoepidermoid carcinoma ,030220 oncology & carcinogenesis ,medicine ,Adenocarcinoma ,business - Abstract
Metastatic tumors to the thyroid gland and direct extension to the thyroid from an adjacent malignancy are uncommon. The tumors that most often metastasize to the thyroid are cancers of the lung, breast, skin (especially melanoma), colon, and kidney. In rare cases, the thyroid metastasis is the initial clinical presentation of the malignancy. With routine and special stains, the distinction from a primary neoplasm of the thyroid is often achievable with fine needle aspiration (FNA). Malignant lymphomas occur as primary malignancies of the thyroid, but they can also involve the thyroid gland secondarily as a manifestation of systemic disease. Some rare epithelial and mesenchymal neoplasms of the thyroid that have a characteristic cytomorphology and/or distinctive immunoprofile can be recognized and diagnosed by FNA. more...
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- 2017
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24. Frozen Section Evaluation of Margin Status in Primary Squamous Cell Carcinomas of the Head and Neck: A Correlation Study of Frozen Section and Final Diagnoses
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Lester J. Layfield, Robert L. Schmidt, Eleanor M. Layfield, and Magda Esebua
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0301 basic medicine ,medicine.medical_specialty ,Pathology ,Concordance ,Sensitivity and Specificity ,Pathology and Forensic Medicine ,03 medical and health sciences ,Intraoperative Period ,0302 clinical medicine ,medicine ,Carcinoma ,Frozen Sections ,Humans ,Sampling (medicine) ,Permanent Section ,Retrospective Studies ,Frozen section procedure ,Original Paper ,business.industry ,Squamous Cell Carcinoma of Head and Neck ,Margins of Excision ,Reproducibility of Results ,medicine.disease ,030104 developmental biology ,Oncology ,Otorhinolaryngology ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Oral and maxillofacial surgery ,Carcinoma, Squamous Cell ,business - Abstract
Frozen section is routinely used for intraoperative margin evaluation in carcinomas of the head and neck. We studied a series of frozen sections performed for margin status of head and neck tumors to determine diagnostic accuracy. All frozen sections for margin control of squamous carcinomas of the head and neck were studied from a 66 month period. Frozen and permanent section diagnoses were classified as negative or malignant. Correlation of diagnoses was performed to determine accuracy. One thousand seven hundred and ninety-six pairs of frozen section and corresponding permanent section diagnoses were obtained. Discordances were found in 55 (3.1%) pairs. In 35 pairs (1.9%), frozen section was reported as benign, but permanent sections disclosed carcinoma. In 21 cases, the discrepancy was due to sampling and in the remaining cases it was an interpretive error. In 20 cases (1.1%), frozen section was malignant, but the permanent section was interpreted as negative. Frozen section is an accurate method for evaluation of operative margins for head and neck carcinomas with concordance between frozen and permanent results of 97%. Most errors are false negative results with the majority of these being due to sampling issues. more...
- Published
- 2017
25. Utilization of ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: The papanicolaou society of cytopathology guidelines for pancreatobiliary cytology
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Ralph H. Hruban, Lester J. Layfield, Martha B. Pitman, Armando C. Filie, Nirag Jhala, Hormoz Ehya, Loren Joseph, and Philippe Vielh
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Pathology ,medicine.medical_specialty ,Histology ,medicine.diagnostic_test ,biology ,business.industry ,Papanicolaou stain ,General Medicine ,Gene mutation ,medicine.disease ,Pathology and Forensic Medicine ,Fine-needle aspiration ,medicine.anatomical_structure ,Biliary tract ,Cytopathology ,biology.protein ,Medicine ,Mesothelin ,Pancreatic cysts ,business ,Pancreas - Abstract
The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound-guided fine-needle aspiration, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and post-biopsy management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings, and synthesis of selected online comments of the draft document. This document presents the results of these discussions regarding the use of ancillary testing in the cytologic diagnosis of biliary and pancreatic lesions. Currently, fluorescence in situ hybridization (FISH) appears to be the most clinically relevant ancillary technique for cytology of bile duct strictures. The addition of FISH analysis to routine cytologic evaluation appears to yield the highest sensitivity without loss in specificity. Loss of immunohistochemical staining for the protein product of the SMAD4 gene and positive staining for mesothelin support a diagnosis of ductal adenocarcinoma. Immunohistochemical markers for endocrine and exocrine differentiation are sufficient for a diagnosis of endocrine and acinar tumors. Nuclear staining for beta-catenin supports a diagnosis of solid-pseudopapilary neoplasm. Cyst fluid analysis for amylase and carcinoembryonic antigen aids in the preoperative classification of pancreatic cysts. Many gene mutations (KRAS, GNAS, VHL, RNF43, and CTNNB1) may be of aid in the diagnosis of cystic neoplasms. Other ancillary techniques do not appear to improve diagnostic sensitivity sufficiently to justify their increased costs. more...
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- 2014
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26. Cytologic Features of Sebaceous Neoplasms of the Parotid Gland: Sebaceous Lymphadenoma and Sebaceous Carcinoma
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Maryna Vazmitsel, Magda Esebua, and Lester J. Layfield
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Pathology ,medicine.medical_specialty ,Parotid Gland Sebaceous Lymphadenoma ,business.industry ,Cytology ,Medicine ,business ,medicine.disease ,Pathology and Forensic Medicine ,Sebaceous carcinoma - Published
- 2019
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27. Critical values: Has their time arrived for cytopathology?
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Lester J. Layfield
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Cancer Research ,medicine.medical_specialty ,Pathology ,Oncology ,business.industry ,Cytopathology ,Cytological Techniques ,Reference values ,Critical illness ,Medicine ,Medical physics ,Differential diagnosis ,business - Published
- 2014
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28. Quality Appraisal of Diagnostic Accuracy Studies in Fine-Needle Aspiration Cytology: A Survey of Risk of Bias and Comparability
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Robert L. Schmidt, Lester J. Layfield, Benjamin L. Witt, and Rachel E. Factor
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Pathology ,medicine.medical_specialty ,Clinical Laboratory Techniques ,business.industry ,media_common.quotation_subject ,Comparability ,Diagnostic accuracy ,General Medicine ,Pathology and Forensic Medicine ,Medical Laboratory Technology ,Quality appraisal ,Key factors ,Fine needle aspiration cytology ,medicine ,Quality (business) ,Medical physics ,business ,media_common - Abstract
Context.—The quality of diagnostic accuracy studies is determined by 2 key factors: risk of bias and comparability. Bias can distort accuracy estimates and poor reporting impairs comparability. While diagnostic accuracy studies for fine-needle aspiration cytology (FNAC) are frequently published, the methodologic issues associated with this body of literature have never been reviewed.Objective.—To assess the quality of design and reporting of diagnostic test accuracy studies in FNAC.Data Sources.—Diagnostic accuracy studies were identified by a Medline (US National Library of Medicine) search. Sixty-four FNAC diagnostic test accuracy studies were randomly selected for structured review with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) survey. Studies were divided between 2 time periods: 2000-2001 and 2009-2011.Conclusions.—Diagnostic test accuracy studies of FNAC suffer from numerous deficiencies in study design, which negatively affect the reliability of accuracy estimates. more...
- Published
- 2013
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29. Risk-Benefit Analysis of Sampling Methods for Fine-Needle Aspiration Cytology: A Mathematical Modeling Approach
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Douglas G. Adler, Kirsten Howard, M. A. Kordy, Lester J. Layfield, Brian J. Hall, Robert L. Schmidt, Schmidt, R, Kordy, M, Howard, Kirsten, Layfield, L, Hall, BJ, and Adler, D
- Subjects
Pathology ,medicine.medical_specialty ,Computer science ,Cytodiagnosis ,Biopsy, Fine-Needle ,Sampling (statistics) ,modeling ,General Medicine ,Models, Theoretical ,Variable sampling ,Risk Assessment ,adverse events ,Increased risk ,Fine needle aspiration cytology ,Sample size determination ,Risk-benefit analysis ,Statistics ,medicine ,Range (statistics) ,Humans ,Variable number ,fine-needle aspiration (FNA) ,risk-benefit analysis - Abstract
The effectiveness of fine-needle aspiration (FNA) increases with the number of needle passes, but needle passes are also associated with increased risk of adverse events. The trade-off between needle passes and adequacy has not been well characterized. Clinical studies are limited because of their inherent variability and limited sample size. We developed mathematical models to compare the performance of a variety of sampling protocols under a wide range of conditions. Specifically, we compared the performance of sampling methods using a fixed number of needle passes with sampling methods using a rapid onsite evaluation (ROSE) with a variable number of needle passes. Variable sampling with ROSE generally required fewer needle passes than fixed sample size policies to achieve a desired adequacy rate. Variable sampling policies using ROSE achieve greater per-case adequacy with fewer needle passes than sampling policies using a fixed number of passes if assessor accuracy is high. more...
- Published
- 2013
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30. Atypical Intradermal Smooth Muscle Neoplasms (Formerly Cutaneous Leiomyosarcomas)
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Howard G. Rosenthal, Lester J. Layfield, Ting Liu, Allie H. Grossmann, Russell A. Ward, Sheryl R. Tripp, R. Lor Randall, Scott R. Florell, Brian J. Hall, Clay J. Cockerell, and Nicholas P. Webber
- Subjects
Adult ,Leiomyosarcoma ,Male ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Histology ,CD34 ,Stain ,Pathology and Forensic Medicine ,Lesion ,Recurrence ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,Humans ,Tensin ,PTEN ,Cutaneous leiomyosarcoma ,Smooth Muscle Tumor ,Aged ,Aged, 80 and over ,Muscle Neoplasms ,biology ,business.industry ,PTEN Phosphohydrolase ,Middle Aged ,Prognosis ,Immunohistochemistry ,Actins ,Staining ,Medical Laboratory Technology ,biology.protein ,Female ,medicine.symptom ,business - Abstract
Atypical intradermal smooth muscle neoplasms (AISMN, formerly known as cutaneous leiomyosarcomas) are uncommon neoplasms, which seem to be remarkable for their excellent prognosis in contrast to their deeper counterparts. The rarity of AISMN has posed a challenge for characterizing the morphologic spectrum, immunohistochemical staining pattern, and behavior. In this study we evaluated the histologic and immunohistochemical features of 20 cases of AISMN. Clinical follow-up was available on 19 out of 20 patients and ranged from 1 to 124 months with an average of 35 months and a median of 20 months with a male predominance (male to female ratio was 2.3:1). Our data show a wide variation in differentiation and atypical features. Among these, the presence of mitotic figures is diagnostically valuable in rendering the final diagnosis. A broad panel of immunohistochemical stains revealed that smooth muscle actin and muscle specific actin, when used in combination, identified smooth muscle differentiation in 100% of the cases. With some caveats, CD34, S100, and CK 5/6 were helpful in ruling out other important cutaneous spindle cell neoplasms. Significantly, loss of phosphatase and tensin homolog (PTEN) staining was seen in the majority of our cases (80%), supporting a role for PTEN loss in the etiology of these lesions. Logistic regression analysis revealed that positive margin status was helpful for predicting recurrence (100% sensitivity and 94% specificity). We conclude that AISMN can have significant morphologic variation and overlap with other spindle cell neoplasms of the skin and that a limited panel of key immunohistochemical stains should be used to distinguish this lesion. The different surgical measures such as wide excision versus Mohs procedure showed a similar clinical outcome. Although the significance of frequent PTEN loss supports a molecular mechanism of tumor genesis, the diagnostic utility of the stain remains to be determined. more...
- Published
- 2013
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31. The role of mast cells in histologically 'normal' appendices following emergency appendectomy in pediatric patients
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Lester J. Layfield, Zhongbo Yang, and Magda Esebua
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Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Inflammation ,Cell Count ,Pathology and Forensic Medicine ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Submucosa ,medicine ,Appendectomy ,Humans ,Mast (botany) ,Mast Cells ,Child ,business.industry ,Infant, Newborn ,Infant ,General Medicine ,medicine.disease ,Mast cell ,Appendicitis ,Immunohistochemistry ,medicine.anatomical_structure ,Acute abdomen ,030220 oncology & carcinogenesis ,Child, Preschool ,030211 gastroenterology & hepatology ,Female ,Tryptases ,medicine.symptom ,business - Abstract
Fifteen percent to 25% of appendices resected for a preoperative diagnosis of acute appendicitis have no neutrophilic infiltration, thus histologically "normal." The discrepancy between clinical presentation and the lack of definite morphologic changes is confounding. It has been indicated that mast cells may play a role in the pathogenesis of the appendicitis-like pain in patients with histologically negative appendices (HNAs). To investigate whether mast cell density (MCD) is increased in pediatric HNAs, we retrieved 50 appendectomy cases (30 HNA and 20 control, ages 2 days-18 years) in our institute in the last 10 years. All cases were stained with mast cell tryptase by immunohistochemistry, and MCD (count/high-power field) was measured in mucosa, submucosa, muscularis, and serosa. Mast cells had the greatest density in the mucosa, followed by the submucosa, in all appendices. MCDs in all 4 layers were significantly higher in HNAs than in the normal controls (mucosa: 46±9 vs 26±11, P more...
- Published
- 2016
32. Gastrointestinal Stromal Tumors: A Guide to the Diagnosis
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Lester J. Layfield, Carlynn Willmore-Payne, and Joseph A. Holden
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Pathology ,medicine.medical_specialty ,Stromal cell ,biology ,GiST ,CD117 ,business.industry ,Imatinib ,medicine.disease ,medicine.disease_cause ,digestive system diseases ,Pathology and Forensic Medicine ,medicine ,biology.protein ,Immunohistochemistry ,Surgery ,Sarcoma ,Differential diagnosis ,Carcinogenesis ,business ,medicine.drug - Abstract
Gastrointestinal stromal tumors (GISTs) have emerged from being a poorly understood and therapeutically refractory sarcoma to a tumor whose biology has not only provided insight into a mechanism of oncogenesis but has also led to a rational basis for therapy. Most GISTs are characterized by KIT protein (CD117) expression and constitutive activating mutations in either the c-kit or platelet-derived growth factor receptor α genes. This information can now be obtained from routine formalin-fixed and paraffin-embedded tissue. Because the correct diagnosis is the key to successful treatment of this tumor, it is incumbent on the pathologist to be familiar with the various gross and histologic patterns shown by these tumors. GISTs range from small incidental stromal nodules to large cystic and solid tumor masses. GISTs show a variety of microscopic patterns and therefore several other tumors enter the differential diagnosis. Fortunately, with an understanding of GIST histology, and with the proper use of immunohistochemistry and molecular analysis, a correct diagnosis can usually be made. In addition to the correct diagnosis, several key attributes of the tumor need to be determined because they provide the basis for proper clinical management. This article summarizes the gross, microscopic, and molecular findings of GISTs, and discusses the differential diagnosis and key attributes of this interesting group of neoplasms. more...
- Published
- 2016
33. Solitary peripheral pulmonary papilloma evaluation on frozen section: A potential pitfall for the pathologist
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Lyska Emerson and Lester J. Layfield
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Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Pathology and Forensic Medicine ,Malignant transformation ,Diagnosis, Differential ,Pulmonary nodule ,medicine ,Frozen Sections ,Humans ,Neoplasm ,Whole Body Imaging ,Diagnostic Errors ,Aged ,Incidental Findings ,Frozen section procedure ,Solitary pulmonary nodule ,Papilloma ,business.industry ,Clinical course ,Solitary Pulmonary Nodule ,Cell Biology ,medicine.disease ,Peripheral ,Treatment Outcome ,Female ,Radiology ,Tomography, X-Ray Computed ,business - Abstract
Endobronchial papilloma is a rare entity that is in the differential for solitary pulmonary nodule. It almost always follows a benign course, with only rare malignant transformation being reported in the squamous variant. No malignant transformation of the glandular variant has been reported to the best of our knowledge, and therefore endobronchial papilloma must be distinguished from more aggressive neoplasms. This distinction is particularly important when one encounters this neoplasm in a peripheral location at frozen section. We report a case of a 65-year-old female with an incidentally discovered solitary peripheral pulmonary nodule identified during a commercial whole-body screening computed tomography (CT) scan. Interval scans revealed a concerning doubling time, and she presented to the surgical service for removal of the mass. Intraoperative frozen section evaluation revealed histologic characteristics favoring a benign neoplasm. Permanent histologic section revealed a glandular papilloma. Over 7 years of follow-up revealed a benign clinical course. more...
- Published
- 2012
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34. Cytomorphologic diagnosis and HPV testing of metastatic and primary oropharyngeal squamous cell carcinomas: A review and summary of the literature
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Jason P. Hunt, Lester J. Layfield, and Elke A. Jarboe
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Oncology ,medicine.medical_specialty ,Pathology ,Histology ,HPV typing ,Cytodiagnosis ,Biopsy, Fine-Needle ,Cell ,Alphapapillomavirus ,Pathology and Forensic Medicine ,Internal medicine ,medicine ,Humans ,Neoplasm Metastasis ,Human papillomavirus ,Head and neck ,Cyclin-Dependent Kinase Inhibitor p16 ,Early Detection of Cancer ,medicine.diagnostic_test ,business.industry ,Papillomavirus Infections ,virus diseases ,General Medicine ,Prognosis ,Neoplasm Proteins ,Oropharyngeal Neoplasms ,stomatognathic diseases ,Hpv testing ,Fine-needle aspiration ,medicine.anatomical_structure ,DNA, Viral ,Carcinoma, Squamous Cell ,Lymph Nodes ,business - Abstract
A significant proportion of squamous cell carcinomas (SCC) of the oropharynx are associated with high-risk human papillomavirus (HPV). These HPV-related carcinomas are prognostically and therapeutically different from traditional SCC of the head and neck. Cervical metastases from head and neck primary SCC are frequently investigated by fine-needle aspiration (FNA). HPV testing of cytologic samples from these lesions would potentially simplify diagnosis and therapeutic planning. This review summarizes current methodologies for HPV testing of FNA specimens and the role of HPV typing in diagnosis, prediction of prognosis, and selection of therapy. Diagn. Cytopathol. 2012;40:491–497. © 2012 Wiley Periodicals, Inc. more...
- Published
- 2012
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35. MDM2 Amplification in Malignant Peripheral Nerve Sheath Tumors Correlates With p53 Protein Expression
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Lester J. Layfield, Sheryl R. Tripp, and Michelle L. Wallander
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Pathology ,medicine.medical_specialty ,In situ hybridization ,Nerve sheath ,Malignancy ,Sensitivity and Specificity ,Nerve Sheath Neoplasms ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Gene duplication ,Biomarkers, Tumor ,medicine ,Peripheral Nerve Sheath Tumors ,Humans ,neoplasms ,In Situ Hybridization, Fluorescence ,Cell Proliferation ,Retrospective Studies ,Neurofibroma ,biology ,Gene Amplification ,Antibodies, Monoclonal ,Proto-Oncogene Proteins c-mdm2 ,General Medicine ,medicine.disease ,enzymes and coenzymes (carbohydrates) ,Medical Laboratory Technology ,Antibodies, Antinuclear ,Mutation ,P53 protein ,Cancer research ,biology.protein ,Mdm2 ,Lipomatous Neoplasm ,Tumor Suppressor Protein p53 ,Neurilemmoma - Abstract
Context.—MDM2 is known to be abnormally upregulated in a variety of human neoplasms, secondary to gene amplification. Assessment of MDM2 amplification is most useful clinically for separating lipomas (nonamplified) from atypical lipomatous neoplasms or well-differentiated liposarcomas (amplified). MDM2 amplification occurs in approximately 7% of all human neoplasms. In this study, we sought to determine the utility of MDM2 amplification for the separation of benign (schwannomas) and malignant peripheral nerve sheath tumors (MPNSTs). The expression of p53 was correlated with MDM2 amplification because early studies have indicated that MDM2 is rarely amplified in MPNSTs that express p53.Objectives.—To determine the percentage of MPNSTs with MDM2 amplification and the specificity of MDM2 amplification for malignancy in nerve sheath tumors.Design.—Fifteen MPNSTs, 14 neurofibromas, and 15 schwannomas were obtained from the files of the Department of Pathology. These cases underwent fluorescent in situ hybridization analysis for the presence of MDM2 amplification. Assessments were also made for cellularity (low or high), percentage of cells staining positively for p53 and MDM2 protein, and percentage of cells staining with MIB-1.Results.—Of 15 MPNSTs, 3 (20%) demonstrated amplification of the MDM2 gene. No neurofibromas or schwannomas demonstrated MDM2 amplification. All 3 MDM2-amplified MPNSTs were positive for p53. Correlation of MDM2 amplification status and p53 immunoreactivity was statistically significant (P = .004).Conclusions.—The low frequency (20%) of MDM2 amplification in our series of MPNSTs demonstrates that MDM2 fluorescent in situ hybridization has limited diagnostic value for the separation of benign schwannomas and MPNSTs. Our study demonstrated a positive correlation (P = .004) between MDM2 amplification and p53 expression. more...
- Published
- 2012
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36. Non-invasive follicular neoplasm with papillary like nuclear features (NIFTP): If it ain't broke, don't fix it. The cytopathologist's dilemma
- Author
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Lester J. Layfield, Virginia A. LiVolsi, and Zubair W. Baloch
- Subjects
0301 basic medicine ,Canada ,Pathology ,medicine.medical_specialty ,Pathology, Clinical ,Histology ,business.industry ,Non invasive ,General Medicine ,Congresses as Topic ,United States ,Pathology and Forensic Medicine ,Dilemma ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Follicular neoplasm ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Humans ,Medicine ,Thyroid Nodule ,business ,Societies, Medical - Published
- 2017
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37. Yolk Sac Tumor of the Thyroid Gland: A Case Report
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Larissa V. Furtado, Theodore J. Pysher, Amy Lowichik, Vasiliki Leventaki, Lester J. Layfield, and Harlan R. Muntz
- Subjects
Pathology ,medicine.medical_specialty ,Extragonadal ,medicine.medical_treatment ,Biopsy, Fine-Needle ,Disease-Free Survival ,Pathology and Forensic Medicine ,Biopsy ,Biomarkers, Tumor ,medicine ,Humans ,Thyroid Neoplasms ,Yolk sac ,Child ,medicine.diagnostic_test ,business.industry ,Thyroid ,Endodermal Sinus Tumor ,Thyroidectomy ,General Medicine ,Endodermal sinus tumor ,medicine.disease ,Combined Modality Therapy ,Treatment Outcome ,medicine.anatomical_structure ,embryonic structures ,Pediatrics, Perinatology and Child Health ,Female ,alpha-Fetoproteins ,Teratoma ,business ,Germ cell - Abstract
Extragonadal yolk sac tumors are uncommon and usually seen in sacrococcygeal, mediastinal, intracranial, and retroperitoneal sites. Yolk sac tumors of the head and neck region are rare, and the few reported cases have arisen in neonates or infants in conjunction with a teratoma or other germ cell tumor subtypes. We report a unique case of a pure yolk sac tumor presenting as a primary lesion in the right thyroid lobe of a 10-year-old girl. The diagnosis was suspected after fine-needle aspiration, and extensive sampling of the thyroidectomy specimen revealed no teratoma or other germ cell tumor. Serum α-fetoprotein levels were markedly elevated 6 days after excision, and imaging disclosed numerous bilateral pulmonary nodules suggestive of metastatic disease but did not reveal a mediastinal mass. The tumor has shown a favorable response to bleomycin, etoposide, and cisplatin chemotherapy. To the best of our knowledge, this is the 1st description of a primary pure yolk sac tumor of the thyroid. more...
- Published
- 2011
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38. Fine-needle aspiration diagnosis of an intraosseous amyloidoma
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Shawn L. Price, Lester J. Layfield, Allie H. Grossmann, Julia R. Crim, Rachel E. Factor, and Rl Randall
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Giant Cells, Foreign-Body ,Male ,Amyloid ,Pathology ,medicine.medical_specialty ,Histology ,Open biopsy ,Biopsy, Fine-Needle ,Plasma Cells ,Plasma cell dyscrasia ,Bone Neoplasms ,Bone and Bones ,Pathology and Forensic Medicine ,Metastatic carcinoma ,medicine ,Humans ,Cell Aggregation ,Amyloidoma ,medicine.diagnostic_test ,business.industry ,Soft tissue ,Amyloidosis ,General Medicine ,Middle Aged ,medicine.disease ,Bone marrow examination ,Fine-needle aspiration ,Tomography, X-Ray Computed ,business ,Amyloid (mycology) - Abstract
Fine-needle aspiration (FNA) is frequently used as the initial diagnostic procedure for the investigation of bone and soft tissue masses. The majority of the lesions detected will represent metastatic carcinoma. Amyloid is a rare cause of a bone mass, with less than 15 published reports describing amyloid deposition within bone. The majority of reported cases involve the vertebral column. We report the finding of a massive amyloidoma of the iliac wing in a 46-year-old man. FNA smears and cell block preparations demonstrated fragments of waxy acellular material misinterpreted as necrotic debris. Subsequent open biopsy established the diagnosis of amyloid with congo red staining demonstrating apple green birefringence. Subsequent workup disclosed the patient to have anemia, hypogammaglobulinemia and trace monoclonal light chain gammopathy. Bone marrow examination revealed CD138a positive lambda restricted plasma cells consistent with plasma cell dyscrasia. Careful attention to the staining characteristics of amyloid in FNA derived material should allow the diagnosis of amyloidoma. 2012. © 2011 Wiley Periodicals, Inc. more...
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- 2011
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39. Detection of Human Papillomavirus Using Hybrid Capture 2 in Oral Brushings From Patients With Oropharyngeal Squamous Cell Carcinoma: Table 1
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Luke O. Buchmann, Mark W. Willis, Brandon G. Bentz, Elke A. Jarboe, Gary D. Ellis, Lester J. Layfield, and Jason P. Hunt
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Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,biology ,business.industry ,Hybrid capture ,virus diseases ,Hypopharyngeal cancer ,General Medicine ,In situ hybridization ,biology.organism_classification ,medicine.disease ,stomatognathic diseases ,Oropharyngeal Neoplasm ,Cytology ,Biopsy ,medicine ,Papillomaviridae ,Oropharyngeal squamous cell carcinoma ,business ,neoplasms - Abstract
Detection of high-risk (HR) human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (SCC) has important prognostic implications; patients exhibit improved survival compared with patients with HPV- SCC. Oral brushing and rinsing samples were obtained from patients with oropharyngeal, oral cavity, or hypopharyngeal SCC and tested for HR-HPV using Hybrid Capture 2 (HC2; QIAGEN, Valencia, CA). HR-HPV in situ hybridization (ISH) was performed on biopsy tissue samples from the same patients. Oral cytologic samples from 16 SCCs were tested by HC2. Biopsy tissue samples were available for ISH in 11 cases. Five oropharyngeal SCCs were HR-HPV+ by ISH and HC2 (oral brushing). Of the oropharyngeal SCCs, 2 were positive by HC2 (oral brushing) and negative or equivocal by ISH. We found that 2 oral cavity carcinomas and 2 hypopharyngeal carcinomas were negative by HC2. One hypopharyngeal cancer was positive by ISH. All oral rinsing samples were negative by HC2. HC2 may be an effective method of determining HR-HPV status in patients with oropharyngeal SCC. more...
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- 2011
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40. Metastatic disease to the pancreas documented by endoscopic ultrasound guided fine-needle aspiration: A seven-year experience
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Sharon L. Hirschowitz, Douglas G. Adler, and Lester J. Layfield
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Adult ,Male ,Endoscopic ultrasound ,Pathology ,medicine.medical_specialty ,Histology ,Adolescent ,Biopsy, Fine-Needle ,Small-cell carcinoma ,Endosonography ,Pathology and Forensic Medicine ,Metastasis ,Young Adult ,Renal cell carcinoma ,medicine ,Humans ,Esophagus ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Fine-needle aspiration ,Medullary carcinoma ,Female ,Pancreas ,business - Abstract
The study was performed to determine the frequency and origin for metastatic disease to the pancreas as found in an endoscopic ultrasound directed fine-needle aspiration series. The records of the Departments of Pathology at the University of Utah School of Medicine and the David Geffen School of Medicine were electronically searched for all fine-needle aspirates obtained from pancreatic masses between January 1, 2002 and March 31, 2010. All cases with a diagnosis of metastatic disease were reviewed and whenever possible correlated with subsequent resection specimens. A total of 17 metastatic malignancies to the pancreas were detected in pancreatic FNAs representing 0.73% of all cases. Primaries included eight renal cell carcinomas, one medullary carcinoma of the thyroid, four lymphomas, one alveolar rhabdomyosarcoma, one squamous cell carcinoma derived from the esophagus, and a second squamous cell carcinoma originating from a lung primary and a small cell carcinoma of the lung. Metastatic renal cell carcinoma was the most frequent metastasis to the pancreas representing 47% of metastatic lesions detected by FNA. The metastatic deposits could be detected in the pancreas as many as 10 years following the original diagnosis and resection of the renal cell carcinoma. more...
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- 2010
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41. Metastatic Pancreatic Adenocarcinoma Presenting as a Large Pelvic Mass Mimicking Primary Osteogenic Sarcoma: A Series of Two Patient Cases
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Kevin B. Jones, Akram M. Shaaban, R. Lor Randall, Sunil Sharma, Lester J. Layfield, Nicholas P. Webber, and Allie H. Grossmann
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Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Bone Neoplasms ,Adenocarcinoma ,Metastasis ,Diagnosis, Differential ,Diagnosis in Oncology ,Pathognomonic ,Humans ,Medicine ,Pelvic Bones ,Osteosarcoma ,business.industry ,Osteoid ,Middle Aged ,Metastatic Pancreatic Adenocarcinoma ,medicine.disease ,Pancreatic Neoplasms ,Oncology ,Sarcoma ,Differential diagnosis ,business - Abstract
Osteogenic sarcoma (ie, osteosarcoma) classically presents as a painful destructive lesion in bone with a large associated soft tissue mass. It has a range of appearances on plain radiographs based on the volume of boney destruction and degree of mineralization within the lesion.1 It is pathologically defined by the production of osteoid matrix by malignant cells. This predilection for bone formation is often apparent on imaging. Although periosteal reactive bone formation in response to a number of aggressive neoplasms and infections can vary in appearance, consistent mineralized bone formation throughout the substance of a mass is considered nearly pathognomonic for osteosarcoma. To our knowledge, there is no case report of a patient presenting initially with a metastasis from pancreatic adenocarcinoma to bone resulting in a large osteogenic mass mimicking osteosarcoma. Although the pelvic girdle has been shown to be a location of skeletal metastases after treatment with surgery and systemic therapy in adenocarcinoma, it is rare for pain resulting from a large osteogenic mass to be the initial presenting symptom.2 more...
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- 2010
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42. Cytologic features of pancreatic intraepithelial neoplasia and pancreatitis: Potential pitfalls in the diagnosis of pancreatic ductal carcinoma
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Elke A. Jarboe and Lester J. Layfield
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Cell Nucleus Shape ,Pathology ,medicine.medical_specialty ,Histology ,endocrine system diseases ,Nuclear Envelope ,medicine.medical_treatment ,Biopsy, Fine-Needle ,Pancreatic Intraepithelial Neoplasia ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Surgical pathology ,medicine ,Atypia ,Humans ,Cell Shape ,Intraductal papillary mucinous neoplasm ,business.industry ,General Medicine ,medicine.disease ,Pancreatic Neoplasms ,Pancreatitis ,Dysplasia ,Cell Nucleus Size ,Pancreatectomy ,Adenocarcinoma ,business ,Carcinoma in Situ ,Carcinoma, Pancreatic Ductal - Abstract
Fine-needle aspiration (FNA) has played a significant role in the diagnosis of pancreatic masses but false-positive diagnoses occur. The Anatomic Pathology files were searched for FNAs of pancreas with subsequent resections. FNAs with a diagnosis of positive for or suspicious for adenocarcinoma followed by a benign resection specimen were reviewed and the surgical pathology and cytology findings correlated. Six cases had a cytologic diagnosis of adenocarcinoma or suspicious for adenocarcinoma but resection specimens were benign. In two cases, a non-invasive intraductal papillary mucinous neoplasm (IPMN) without significant dysplasia was present surrounded by foci of pancreatic intraepithelial neoplasia (PanIN). In both cases, the degree of atypia within the IPMN was less than that seen cytologically. The nuclear features of the PanIN overlapped those seen in the smears. In two cases, a neuroendocrine neoplasm was present accompanied by multifocal PanIN. The cytologic features of the neuroendocrine neoplasm did not correlate with the material cytologically diagnosed as adenocarcinoma. The cytologically atypical epithelium was similar to the PanIN. Two diagnoses of adenocarcinoma were made cytologically but the pancreatectomy specimens revealed pancreatitis with reactive atypia. Cytologic diagnosis of pancreatic adenocarcinoma has high specificity. Six cytologic misdiagnoses of adenocarcinoma occurred in 105 patients. The cytologic features of these misdiagnoses correlated with histopathologic changes of intermediate to high-grade PanIN or marked reactive atypia in severe pancreatitis. PanIN may be an under recognized, but significant source of false-positive results. Diagn. Cytopathol. 2011. © 2010 Wiley-Liss, Inc. more...
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- 2010
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43. Follicular Variant of Papillary Carcinoma: Reproducibility of Histologic Diagnosis and Utility of HBME-1 Immunohistochemistry and BRAF Mutational Analysis as Diagnostic Adjuncts
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Harshwardhan M. Thaker, Joseph A. Holden, Elke A. Jarboe, Ting Liu, Lester J. Layfield, Lyska Emerson, Sheryl R. Tripp, and Michelle L. Wallander
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Proto-Oncogene Proteins B-raf ,endocrine system ,Pathology ,medicine.medical_specialty ,Histology ,DNA Mutational Analysis ,Sensitivity and Specificity ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Adenocarcinoma, Follicular ,Biomarkers, Tumor ,Carcinoma ,Humans ,Medicine ,Thyroid Neoplasms ,Observer Variation ,Reproducibility ,business.industry ,Thyroid ,Reproducibility of Results ,medicine.disease ,Immunohistochemistry ,Carcinoma, Papillary ,Medical Laboratory Technology ,medicine.anatomical_structure ,Focal Nodular Hyperplasia ,Adenocarcinoma ,Papillary carcinoma ,business ,Follicular variant - Abstract
Despite the recognition of the follicular variant of papillary carcinoma of the thyroid (FVPTC) for over 50 years, reproducibility of this diagnostic category has remained poor. Architectural features have been of variable utility as some FVPTC seem encapsulated, whereas others are multifocal and may be confused with nodular hyperplasia. Nuclear features are important for diagnosis of FVPTC, but some authors have discounted the utility of nuclear grooves and inclusions. More recently, BRAF and HBME-1 (Human Bone Marrow Endothelial Cell-1) have been suggested as markers for FVPTC.To investigate the frequency of BRAF mutations and HBME-1 immunopositivity, in a series of FVPTCs in which the diagnosis was established by 100% consensus among a panel of 6 surgical pathologists.Twenty-eight specimens with an original diagnosis of FVPTC and 10 cases with other diagnoses were obtained from the surgical pathology files of the University of Utah School of Medicine. All specimens were independently reviewed by 6 surgical pathologists. Tissue blocks were analyzed for BRAF exon 15 mutations and HMBE-1 expression.Complete agreement among pathologists for the diagnosis of FVPTC was obtained in 28.6% (8/28) of cases originally diagnosed as FVPTC. Mutations in BRAF exon 15 were found in 25% (2/8) of cases with a 100% consensus diagnosis of FVPTC and 32% (6/19) of cases unanimously diagnosed as a type of papillary carcinoma (classic or follicular variant). HBME-1 was expressed in 87.5% (7/8) of lesions with a 100% consensus diagnosis of FVPTC and 84.2% (16/19) of lesions with a unanimous diagnosis of a type of papillary carcinoma of the thyroid (classic or follicular variant).Interobserver agreement for the diagnosis of FVPTC is poor and testing for the BRAF mutation is only marginally helpful because a minority of FVPTCs possess the mutation. HBME-1 expression when coupled with a BRAF mutation, results in 100% specificity but low sensitivity for the presence of papillary carcinoma of the thyroid including the follicular variant. more...
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- 2010
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44. Fibromatosislike Metaplastic Carcinoma of the Breast as a Diagnostic Pitfall for Fine Needle Aspiration Cytology
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Brian T. Collins, Lester J. Layfield, and Elke A. Jarboe
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Pathology ,medicine.medical_specialty ,Histology ,Suspicious for Malignancy ,medicine.diagnostic_test ,business.industry ,Metaplastic carcinoma ,medicine.medical_treatment ,Lumpectomy ,General Medicine ,medicine.disease ,Pathology and Forensic Medicine ,Breast cancer ,Biopsy ,Carcinoma ,medicine ,Breast disease ,Nuclear atypia ,skin and connective tissue diseases ,business - Abstract
UNLABELLED BACKGROUND Metaplastic carcinomas of the breast are uncommon, and most display marked cellular atypia. Recently, a low grade fibromatosis-like metaplastic carcinoma was found and displayed little nuclear atypia. CASE A 74-year-old woman presented with a 2.5-cm, palpable breast nodule. Mammogram was reported as suspicious for malignancy. Cytologic examination revealed smears of low cellularity with most cells lying in clusters and having a round or oval shape. Rare cells had a "spindle" shape. Nuclear features were low grade. Rare individual cells had retained cytoplasm. Lumpectomy revealed a fibromatosis-like metaplastic carcinoma. CONCLUSION Cytologically, fibromatosis-like metaplastic carcinomas are low grade lesions producing smears of relatively low cellularity. Separation from ductal carcinomas is necessary because fibromatosis-like metaplastic carcinomas rarely metastasize to lymph nodes. more...
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- 2010
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45. Histologic, Immunohistochemical, and Molecular Classification of 52 IPMNs of the Pancreas
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Barbara Chadwick, Joseph A. Holden, Carlynn Willmore-Payne, Sharon L. Hirschowitz, Lester J. Layfield, and Sheryl R. Tripp
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Pathology ,medicine.medical_specialty ,Histology ,endocrine system diseases ,Epithelium ,Pathology and Forensic Medicine ,Molecular classification ,Intestinal Neoplasms ,Biomarkers, Tumor ,medicine ,Humans ,business.industry ,Gene Expression Profiling ,Mucin ,Mucins ,Epithelial Cells ,Classification ,Invasive ductal carcinoma ,Immunohistochemistry ,Neoplasm Proteins ,Staining ,Medical Laboratory Technology ,medicine.anatomical_structure ,Mutation ,Pancreas ,business ,Carcinoma, Pancreatic Ductal ,Genes, Neoplasm - Abstract
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas account for approximately 5% of pancreatic neoplasms. Prognosis is superior to that of pancreatic invasive ductal carcinoma. IPMNs reveal a variety of epithelial linings expressing different mucin staining patterns and may progress along different oncogenic pathways.Fifty-two IPMNs were studied for expression of MUC1, MUC2, p16, p21, HER2, cyclin D1, and p53 protein and for mutations in K-ras, HER2, p53, EGFR, and BRAF genes. The cases were evaluated for dysplasia, presence of invasion, and morphology of lining epithelium.Twenty-six IPMNs appeared intestinal (IN). Five were low, 12 moderate, and 9 high grade. K-ras mutations were found in 15, EGFR mutations in 2, and BRAF mutation in 1. Seven cases were pancreaticobiliary (PB) and all showed moderate to high-grade dysplasia. Six K-ras mutations and 2 p53 mutations were found in PB tumors. p53 mutations were in cases with high-grade dysplasia. Nineteen IPMNs demonstrated a gastric foveolar (GF) pattern. The majority of GF cases had low or moderate dysplasia. Sixteen revealed K-ras mutations and 1 case each demonstrated a HER2 or p53 mutation. Five IPMNs revealed invasive adenocarcinoma, including a colloid carcinoma from an IN type epithelium.IN pattern IPMNs were the most common. Mixed histology was common. K-ras mutations were most common, but did not correlate with dysplasia. p53 mutations were seen in 6% of cases (only in GF and PB subtypes). A HER2 mutation was found in a GF IPMN. EGFR and BRAF mutations were restricted to IN IPMNs. These findings suggest the possibility of alternate pathways for carcinogenesis between epithelial subtypes of IPMNs. more...
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- 2009
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46. A gastrointestinal stromal tumor of the stomach morphologically resembling a neurofibroma: demonstration of a novel platelet-derived growth factor receptor α exon 18 mutation
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Carlynn Willmore-Payne, Robert E. Glasgow, Ting Liu, Joseph A. Holden, and Lester J. Layfield
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Pathology ,medicine.medical_specialty ,Stromal cell ,Gastrointestinal Stromal Tumors ,DNA Mutational Analysis ,Biology ,Polymerase Chain Reaction ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Exon ,Germline mutation ,Growth factor receptor ,Gastrectomy ,Stomach Neoplasms ,Biomarkers, Tumor ,medicine ,Humans ,Neurofibroma ,Stromal tumor ,Platelet-Derived Growth Factor ,Cancer ,DNA, Neoplasm ,Exons ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Mutation ,Cancer research ,biology.protein ,Female ,Platelet-derived growth factor receptor - Abstract
Summary Gastrointestinal stromal tumors are increasingly being recognized because of their characteristic expression of KIT (CD 117). Most KIT-positive gastrointestinal stromal tumors have activating mutations in the c-kit gene. A subgroup of gastrointestinal stromal tumors are negative for KIT expression, and in these tumors, activating mutations in platelet-derived growth factor receptor α are common. Most platelet-derived growth factor receptor α mutation–positive gastrointestinal stromal tumors show an epithelioid histology and are located in the stomach. Herein, we describe an unusual gastric stromal tumor. The tumor was negative for KIT expression and the morphology did not show an epithelioid pattern but rather was composed of bland spindle cells reminiscent of a neurofibroma. Molecular analysis revealed a somatic mutation in platelet-derived growth factor receptor α exon 18 (D842F). Aside from demonstrating a new platelet-derived growth factor receptor α mutation, this case illustrates the usefulness of molecular testing as a diagnostic tool and clearly indicates the wide range of morphology that can be observed in gastrointestinal stromal tumors. more...
- Published
- 2008
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47. Histopathologic Review of Previously Negative Prostatic Core Needle Biopsies Following a New Diagnosis of Adenocarcinoma of the Prostate by Core Needle Biopsies: Implications for Quality Assurance Programs
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Lester J. Layfield and Jay Patel
- Subjects
Microbiology (medical) ,Pathology ,medicine.medical_specialty ,Histology ,quality assurance ,core needle biopsy ,Malignancy ,diagnostic errors ,Pathology and Forensic Medicine ,Surgical pathology ,Prostate ,Biopsy ,lcsh:Pathology ,medicine ,Original Research ,Intraepithelial neoplasia ,prostate ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Squamous intraepithelial lesion ,medicine.anatomical_structure ,Cytopathology ,Adenocarcinoma ,business ,lcsh:RB1-214 - Abstract
Programs for quality assurance are increasingly important in surgical pathology. Many quality assurance (QA) techniques for surgical pathology were adopted from procedures introduced in cytopathology. Surgical pathology specimens have diminished in size such that the majority of diagnostic biopsies of prostatic lesions are now core needle biopsies. These specimens raise issues similar to those of cytology specimens, including concerns regarding adequacy and the representative nature of the biopsy. Due to sample size, some neoplasms may not be diagnosed on initial biopsy, raising concerns regarding false negative results. Cytopathologists have instituted QA procedures including review of all previously negative slides received within five years prior to the new diagnosis of high grade squamous intraepithelial lesion or gynecologic malignancy. No such requirement exists in surgical pathology for review of core biopsies. The Department of Pathology at the University of Utah instituted a QA policy requiring review of prior negative prostatic needle biopsies following a new diagnosis of prostatic adenocarcinoma. We reviewed five years of QA records of prostate needle biopsy review. During this time, nine hundred and fifty-eight core biopsy sets were performed. Two hundred and ninety-five of these contained at least one biopsy with a diagnosis of adenocarcinoma. Two hundred and eight patients had a prior set of prostatic needle biopsies with a diagnosis of adenocarcinoma. The remaining 87 had prior biopsies with either a diagnosis of prostatic intraepithelial neoplasia (23), small atypical acinar proliferation (21) or no evidence of malignancy (43). QA review of these 87 cases revealed two biopsies which revealed foci of adenocarcinoma. Both had been initially diagnosed as no evidence of malignancy. The false negative rate for core biopsy was 0.68%. In an additional twenty-one cases, microscopic foci of atypical small acinar proliferations were found in core biopsies antedating the positive core biopsy (7.1%). more...
- Published
- 2008
48. Fine-needle aspiration cytology versus core-needle biopsy for major salivary gland lesions
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Andrew Wilson, Rachel E. Factor, Robert L. Schmidt, Lester J. Layfield, Benjamin L. Witt, and Brian J. Hall
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Core needle ,education.field_of_study ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Population ,Disease spectrum ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Disease severity ,Fine needle aspiration cytology ,030220 oncology & carcinogenesis ,Major Salivary Gland ,Biopsy ,medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Radiology ,medicine.symptom ,education ,business - Abstract
This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the diagnostic accuracy of fine-needle aspiration and core-needle biopsy for the diagnosis of tumours (neoplastic versus non-neoplastic) in major salivary glands. To determine the diagnostic accuracy of fine-needle aspiration and core-needle biopsy for the diagnosis of malignant tumors in major salivary glands (i.e. the conditional probability that a lesion is malignant given that it is neoplastic). To identify factors that may affect the diagnostic accuracy of fine-needle aspiration for the diagnosis of major salivary gland lesions. There are many factors that could potentially affect the accuracy of the testing process. These include study-level factors (location, time period of study and setting: academic center versus community), disease spectrum (distribution of lesion types, distribution of glands), index test factors (too many to list), reference test factors and population factors (referral patterns, disease severity). While it is reasonable to suppose that any of these factors could affect FNAC test accuracy, there are few experimental data to guide the selection of factors for investigation. Also, in our experience, FNAC accuracy studies generally suffer from variable and incomplete reporting (Schmidt 2011; Schmidt 2011b). Thus, it is unlikely that studies would provide sufficient data to support an analysis of heterogeneity, even if a large number of studies were included. Thus, we do not expect that investigations of heterogeneity are likely to be feasible. more...
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- 2016
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49. Prognostic markers in smear preparations for pancreatic endocrine neoplasms: A cytomorphologic study and statistical analysis of 20 potential prognostic features
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Lester J. Layfield, Robert L. Schmidt, Magda Esebua, and Jack Campbell
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Pathology ,medicine.medical_specialty ,Proliferation index ,business.industry ,lcsh:Cytology ,Papanicolaou stain ,grading ,Logistic regression ,Classification ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Cytopathology ,030220 oncology & carcinogenesis ,Endocrine neoplasm ,medicine ,cytology ,Endocrine system ,030211 gastroenterology & hepatology ,Statistical analysis ,lcsh:QH573-671 ,pancreatic endocrine tumors ,business ,Grading (tumors) ,Research Article - Abstract
Background: Papanicolaou Society of Cytopathology guidelines place low- and intermediate-grade pancreatic endocrine tumors into the “neoplastic, other” category whereas high-grade pancreatic endocrine tumors are placed in the “malignant” category. No attempt was made to stratify pancreatic endocrine tumors in the “neoplastic, other” category by likelihood for metastases. Histologically, pancreatic endocrine tumors are divided into well, intermediate, and poorly differentiated examples based on mitotic count and Ki-67 proliferation index (PI). PI has been used in the evaluation of cytologic specimens utilizing cell block material. Unfortunately, cell block material may not always be available for analysis, and little data exists as to cytomorphologic features in smear preparations which might distinguish between low- and intermediate-grade endocrine neoplasms and predict metastases. Methods: We studied 36 cases of Diff-Quik stained smear preparations for 20 morphologic features to determine which best-classified cases into poor and not poor outcome categories. Hierarchical logistic regression analysis was used to determine associations between the morphologic features and outcomes. Results: Absolute agreement between raters ranged from 51% to 97% across the 20 morphologic features. About 12 of the 20 morphologic features showed statistically significant associations with poor outcome. Mitoses, irregular nuclear membranes, and 3-fold variation in nuclear size are the best discriminators between poor and not poor outcomes. Conclusions: A scoring system was developed utilizing mitoses, irregular nuclear membranes, and 3-fold variation in nuclear size to divide smears of pancreatic endocrine tumors into poor and not poor outcome groups. The scoring system achieved 84% accuracy in separating cases into poor and not poor outcomes. more...
- Published
- 2015
50. Neoplastic and tumor-like lesions of bone
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Yaxia Zhang, Andrew E. Rosenberg, Lester J. Layfield, and G. Petur Nielsen
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Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Aneurysmal bone cyst ,medicine.disease ,Phosphaturic mesenchymal tumor ,Surgical pathology ,Nonossifying fibroma ,Bone scintigraphy ,Cytopathology ,Primitive neuroectodermal tumor ,medicine ,business ,Grading (tumors) - Published
- 2015
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