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1.
Diagn Cytopathol ; 52(3): 163-170, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38095142

RESUMO

BACKGROUND: PD-L1 immunoexpression in head and neck squamous-cell carcinoma (HNSCC) determines immunotherapy eligibility. Patients are often diagnosed using fine-needle aspiration (FNA) of metastatic lymph nodes, however, the cytohistologic correlation of the combined positive score (CPS) is largely unknown. METHODS: This study retrospectively identified 96 paired histologic (HS) and cytologic specimens (CyS), between 2016 and 2020, diagnosed with HNSCC. Cases with <100 tumor cells (n = 54) or missing block(s) (n = 8) were excluded. All 34 case pairs were scored with CPS using the PD-L1 22C3 pharmDx assay at clinically relevant cut-offs of <1%, 1%-19%, and ≥20% independently by three observers blinded to the case pairs (CyS with corresponding HS). RESULTS: The CPS (<1/1-19/≥20) for CyS and HS were as follows: 10(29.4%)/10(29.4%)/14(41.2%) and 2(5.9%)/13(38.2%)/19(55.9%), respectively. There was fair overall cytohistologic agreement (OA) of 76.5% (k = 0.261) at the CPS cut-off of 1. The OA did not differ significantly between site-matched (n = 13) and -unmatched (n = 21) case pairs (p = .4653). CyS has a specificity and positive predictive value (PPV) of 100% but a negative predictive value (NPV) of only 20% as compared to its paired HS. CONCLUSIONS: Our study demonstrates fair CPS cytohistologic correlation in HNSCC specimens using the PD-L1 IHC 22C3 pharmDx assay with high PPV but low NPV. This suggest that determining PD-L1 status in FNA specimens can play an important role in the clinical management of HNSCC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Biópsia por Agulha Fina , Estudos Retrospectivos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Imuno-Histoquímica , Biomarcadores Tumorais/metabolismo
2.
Lung Cancer ; 171: 42-46, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35907387

RESUMO

BACKGROUND: Testing for tumor programmed death ligand-1 (PD-L1) expression was initially developed with histology specimens in non-small cell lung cancer (NSCLC). However, cytology specimens are widely used for primary diagnosis and biomarker studies in clinical practice. Limited clinical data exist on the predictiveness of cytology-derived PD-L1 scores for response to immune checkpoint inhibitor (ICI) therapy. METHODS: We reviewed all NSCLC specimens clinically tested at the University Health Network (UHN) for PD-L1 with 22C3pharmDx, from 01/2013 to 04/2021. Treatment outcomes in patients treated with single agent ICI therapy were reviewed and compared according to cytology- and histology-derived PD-L1 scores. RESULTS: We identified 494 and 1942 unique patients with cytology- and histology-derived tumor proportion scores, respectively, during the study period. Informative testing rates were 95 % vs 98 % for cytology and histology, respectively. Clinical data were available for 152 patients treated with single agent ICI: 61 cytology and 91 histology. Overall response rates (ORR) were similar for cytology and histology (36 % vs 34 %; p = 0.23), as well as median progression free survival (PFS) (4.9 vs 4.2 months; p = 0.99) and overall survival (23.4 vs 19.7 months; p = 0.99). The results remained similar even after adjusting for PD-L1 expression levels and line of ICI treatment (PFS HR 1.15; 95 %CI 0.78-1.70; p = 0.47). CONCLUSIONS: Treatment outcomes to single agent ICI based on cytology-derived PD-L1 scores were comparable to histology controls. Our results support PD-L1 biomarker testing on both cytology and histology specimens.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia
3.
Urol Oncol ; 40(7): 346.e9-346.e16, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35393232

RESUMO

BACKGROUND: Urine cytology and cystoscopy are routinely employed during follow-up of patients after trimodal therapy (TMT) for muscle-invasive bladder cancer (MIBC). The significance of positive or equivocal cytology without visible disease recurrence on cystoscopy during follow-up is unknown, and studies informing outcomes in this scenario are lacking. This study aims to investigate the temporal trends of positive/equivocal cytology in the absence of visible disease recurrence and the association with bladder cancer recurrence and survival outcomes. METHODS: One hundred and twenty-nine patients with available post-TMT cytology data and negative cystoscopy from a single academic institution between 2002 and 2017 with a median follow-up of 3.4 (range 0.1-14.2) years were analyzed. Cytology results, first post-TMT cytology positive/equivocal (CP) and negative (CN), were evaluated for association with disease recurrence and survival. Kaplan. Meier and competing risks methods were used to assess time-to-negative cytology in CP patients with ≥2 interval post-TMT cytology results (n = 33), time-to-recurrence, and disease-specific mortality (DSM) stratified by first post-TMT cytology result. RESULTS: At first follow-up (6-8 weeks post-TMT completion), CP was observed in 41 (32%) and CN in 88 (68%) of patients. With further follow-up of CP patients with ≥2 interval post-TMT cytology results, the probability of developing negative cytology was 57% (95% CI 42, 77) at 6 months post-TMT, and the median time-to-negative cytology was 3.2 months (95% CI 2.99, 5.80). The median time-to-recurrence was reduced in CP patients compared to CN (24.3 vs. 78.1 months, p = 0.1), corresponding with an apparent increase in the cumulative incidence of recurrence rate at 3 years in the CP vs. CN group (62% vs. 42%, p = 0.1). No significant difference was observed in the 3-year DSM rates. On univariable analysis, the hazards of recurrence and DSM for patients with CP were 1.5 (95% CI 0.9, 2.5, p = 0.1) and 2.1 (95% CI 0.9, 4.7, p = 0.07) respectively. CONCLUSION: This is the first study to investigate the significance of a positive/equivocal cytology without visible disease following TMT for MIBC. Positive cytology is common and does not preclude subsequent negative cytology supporting a watchful waiting approach rather than proceeding immediately to biopsy. However, cytology that remains positive at subsequent follow-up may be associated with adverse recurrence and survival outcomes.


Assuntos
Neoplasias da Bexiga Urinária , Cistoscopia/métodos , Humanos , Músculos/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Neoplasias da Bexiga Urinária/patologia
4.
Cancer Treat Res Commun ; 31: 100534, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35278845

RESUMO

OBJECTIVES: Standard molecular testing for patients with stage IV non-small cell lung cancer (NSCLC) in the Canadian publicly funded health system includes single gene testing for EGFR, ALK, and ROS-1. Comprehensive genomic profiling (CGP) may broaden treatment options for patients. This study examined the impact of CGP in a publicly funded health system. METHODS: Consenting patients with stage IV NSCLC without known targetable alterations underwent CGP on diagnostic samples. Patients that had progressed on targeted therapy were also eligible. The CGP assay was a hybrid capture next generation sequencing (NGS) panel (Oncomine Comprehensive Assay Version 3, ThermoFisher). The number of actionable alterations, changes in treatment, clinical trial eligibility and costs as a result of CGP were evaluated and patient willingness-to-pay. RESULTS: Of 182 screened patients,134 (74%) had successful CGP testing. Twenty percent had received prior targeted therapy. Incremental actionable alterations were identified in 31% of patients. The most common novel targets identified were mutations in ERBB2 (exon 20 insertions), MET (exon 14 skipping) and KRAS (G12C). At data cut off (31/12/2020), 16% of patients had a change in treatment as a result of CGP. Additional clinical trial options were identified for 75% of patients. The incremental direct laboratory cost for CGP beyond public reimbursement for single gene tests was $747 CAD/case. CONCLUSION: CGP identifies additional actionable targets beyond single gene tests with a direct impact on patient treatment and increased clinical trial eligibility. These benefits highlight the value of CGP in patients with NSCLC in public health systems.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Canadá , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Atenção à Saúde , Genômica , Humanos , Neoplasias Pulmonares/tratamento farmacológico
5.
J Am Soc Cytopathol ; 11(3): 142-153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35305954

RESUMO

INTRODUCTION: Cytology samples are frequently relied upon for the diagnosis of advanced cancer such as lung cancer. As the recommendations for solid malignancies biomarker testing continue to expand, it becomes increasingly important to efficiently utilize limited specimens to minimize the need for additional sampling and its associated risks and costs. MATERIALS AND METHODS: We performed molecular testing on fresh or CytoLyt-fixed supernatants derived from fine needle aspirates (FNAs) and compared its performance against the clinical specimen (including formalin-fixed paraffin-embedded cell blocks, residual PreservCyt and fresh samples). Supernatants were assessed for cellularity using Field-stained Cytospin (CS) preparations. RESULTS: There was overall almost perfect agreement (41/45 cases, K = 0.822) and substantial to almost perfect agreement in molecular testing results of clinically actionable variants between fresh (20/23 cases, Κ = 0.742) and CytoLyt-fixed (21/22 cases, Κ = 0.908) and its clinical specimen counterpart. Interestingly, CS examination of the supernatants revealed viable tumor cells. Centrifugation for 1 minute at 300 rpm is optimal for overall or tumor cellularity recovery. Delayed molecular testing after 3, 4 and 7 days at 4 degrees Celsius showed identical molecular results. CONCLUSIONS: We validated the use of supernatants derived from FNA cytology samples as a substrate for molecular testing using next-generation sequencing and other molecular techniques.


Assuntos
Neoplasias Pulmonares , Biópsia por Agulha Fina/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Neoplasias Pulmonares/diagnóstico , Técnicas de Diagnóstico Molecular , Manejo de Espécimes/métodos
6.
Radiol Case Rep ; 17(3): 775-778, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34976267

RESUMO

Worldwide, many vaccines have been developed in response to the COVID-19 pandemic. Unilateral reactive axillary adenopathy related to the COVID-19 vaccine is a well-known occurrence. In addition, axillary edema has also been observed following COVID-19 vaccinations in patients undergoing breast MRI, and radiologists need to be aware of this possibility to avoid performing unnecessary work-up that can be costly to the health care system and be stressful for patients.

7.
Cancer Cytopathol ; 129(11): 907-913, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34157791

RESUMO

BACKGROUND: Testing for BRCA1/2 gene alterations in patients with high-grade serous carcinoma (HGSC) is a critical determinant of treatment eligibility for poly(adenosine diphosphate-ribose) polymerase inhibitors in addition to providing vital information for genetic counselling. Many patients present with effusions necessitating therapeutic drainage, and this makes cytologic specimens (CySs) the initial diagnostic material for HGSC, often before histologic sampling. Initiating somatic BRCA testing on a CyS allows the BRCA status to be determined sooner, and this affects clinical management. METHODS: Retrospectively, 8 cases of formalin-fixed, paraffin-embedded (FFPE) CySs of peritoneal or pleural fluid from patients with HGSC and known BRCA1/2 alterations previously established by the testing of FFPE surgical specimens (SpSs) underwent next-generation sequencing (NGS). Prospectively, 11 cases of peritoneal or pleural fluid from patients with HGSC but an unknown BRCA1/2 status underwent NGS with fresh, alcohol-fixed, and FFPE CySs, and they were compared with subsequent NGS on 4 SpSs. RESULTS: CySs yielded high-quantity and high-quality DNA for NGS analysis when sufficient tumor cellularity was present. Fresh, alcohol-fixed, and FFPE CySs were all suitable for NGS and provided identical NGS results. SpS and CyS BRCA testing was concordant in 10 of 12 cases. The 2 discordant cases showed low tumor cellularity and quality in the CyS and the SpS, respectively. CONCLUSION: Effusion CySs of HGSC are excellent sources for NGS testing for BRCA1/2 genetic alterations when sufficient tumor cellularity is present. Fresh, alcohol-fixed, and FFPE CySs are equivalent for NGS of BRCA1/2. NGS testing of HGSC CySs demonstrates good concordance with SpSs for the BRCA1/2 status.


Assuntos
Carcinoma , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Estudos Retrospectivos
8.
Am J Clin Pathol ; 156(6): 1155-1161, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34160017

RESUMO

OBJECTIVES: Phone calls to the microbiology laboratory can be to clarify culture results and provide education, but those calls also interrupt laboratory workflow. We characterized calls that the laboratory received and developed targeted comments to educate providers. METHODS: Calls were logged and characterized, and we developed comments to address common call subjects. We applied the new comments to cultures and logged calls over the same interval the subsequent year. Data before and after implementation were analyzed. RESULTS: Call volume decreased from 496 calls to 419 calls after implementation. There was a significant difference in level of training among callers (P < .005), but the nature of the calls did not change. Laboratory response showed an increase in release of previously generated data (eg, suppressed susceptibility results). Comments specifically developed to address intrinsic antibiotic resistance and common susceptibility patterns did not decrease call volume. CONCLUSIONS: Implementation of comments in the laboratory information system decreased call volume, but targeted comments were less effective than anticipated.


Assuntos
Sistemas de Informação em Laboratório Clínico , Testes Diagnósticos de Rotina , Hospitais , Humanos , Laboratórios
9.
Am J Clin Pathol ; 147(5): 525-535, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28398539

RESUMO

OBJECTIVES: The aim of this study was to determine the prevalence of bile cast nephropathy (BCN) in autopsied cirrhotic patients and to correlate BCN with clinical and laboratory data to direct attention to this underrecognized renal complication of liver failure. METHODS: We assessed 114 autopsy cases of cirrhosis for the presence of renal intratubular bile casts using Hall stain for bile. Presence of bile casts was correlated with etiology of cirrhosis, clinical and laboratory data, and histologic findings. RESULTS: Bile casts were identified in 55% of cases. The most common etiology of cirrhosis was hepatitis C virus (HCV) infection (52%), and serum creatinine ( P = .02) and serum urea nitrogen ( P = .01) were significantly higher in the Hall-positive group. Conjugated bilirubin was below 20 mg/dL in 90%, and levels below 10 mg/dL were noted in 80% of cases. CONCLUSIONS: To our knowledge, this is the largest study of BCN in human subjects and a first report describing the association of BCN with HCV-related cirrhosis. We demonstrated that in the face of protracted chronic hyperbilirubinemia, bile casts are formed at much lower bilirubin levels than previously thought. Furthermore, we proposed an algorithm to assist in better identification of bile casts.


Assuntos
Hiperbilirrubinemia/complicações , Nefropatias/epidemiologia , Nefropatias/etiologia , Cirrose Hepática/complicações , Adulto , Idoso , Autopsia , Bile , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
10.
J Am Soc Cytopathol ; 6(5): 180-184, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31043240

RESUMO

INTRODUCTION: In 2013, our laboratory introduced Roche cobas high-risk human papillomavirus (HRHPV) testing, which includes limited HPV genotype reporting. The shift from Hybrid Capture II (HC2) HPV testing to Roche led to an observed increase in biopsies for patients with negative Papanicolaou tests with positive HRHPV. MATERIALS AND METHODS: We conducted a retrospective review of data from our facility to examine biopsies conducted on patients with negative Papanicolaou tests and positive HRHPV. We compared data from 2012 (HC2) to 2015 after implementation of Roche cobas platform. RESULTS: In 2012, 37 biopsies were performed on patients with negative Papanicolaou test and positive HRHPV, out of 82,721 Papanicolaou tests (0.045%). In 2015, the number of biopsies performed on patients with negative Papanicolaou test and positive HRHPV test was 281, out of 115,104 Papanicolaou tests (0.244%; P < 0.001). Of these, 141 had HPV type 16 or 18, and 140 had "other" HRHPV types. We observed an increased detection rate of high-grade squamous intraepithelial lesion (HSIL) or greater lesions (5.4% in 2012 to 8.9% in 2015), but it was not statistically significant (P = 0.398). Fifteen HSIL or greater lesions were found in women with types 16 or 18 (5.3%) and 10 were found in women with "other" HRHPV types (3.6%). CONCLUSION: The introduction of HRHPV testing with type reporting is associated with a marked increase in the number of women undergoing colposcopy and biopsy for HRHPV despite negative cytology. Half of these have a HRHPV type other than type 16 or 18, despite recommendations to repeat co-testing instead.

11.
Am J Hosp Palliat Care ; 28(3): 176-82, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20834033

RESUMO

Planning for end-of-life (EOL) care can result in better patient outcomes and lowered health care costs. We hypothesized that knowledge and experiences with EOL care would influence patients' EOL planning (i.e., health care decisions, hospice use). Using an observational, cross-sectional design, we recruited a community sample of 331 South Floridians aged 18 to 84 (M = 44 years, SD = 14.95) to complete a questionnaire examining knowledge and opinions on EOL issues. Regression analyses showed that prior knowledge of living wills and hospice services were associated with more favorable attitudes toward hospice care, preference for limited medical interventions at EOL, and more comfort in communicating about death and dying. Patient education on EOL care may increase hospice use, enhance EOL planning, and improve patient outcomes.


Assuntos
Planejamento Antecipado de Cuidados , Atitude Frente a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Cuidados Paliativos na Terminalidade da Vida/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Fatores Socioeconômicos , Inquéritos e Questionários , Assistência Terminal/psicologia , Adulto Jovem
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