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“Atypia” on Biopsy: Possible Precursor to Lung Cancer?

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“Atypia” on Biopsy: Possible Precursor to Lung Cancer? Article Clinical Implications of “Atypia” on Biopsy: Possible Precursor to Lung Cancer? Denise Albano 1,*, Lee Ann Santore 2 , Thomas Bilfinger 1, Melissa Feraca 1, Samantha Novotny 2 and Barbara Nemesure 1 1 Lung Cancer Evaluation Center at Stony Brook University Hospital, Stony Brook, NY 11790, USA; Thomas.Bilfi[email protected] (T.B.); [email protected] (M.F.); [email protected] (B.N.) 2 Renaissance School of Medicine at Stony Brook University, Stony Brook, NY 11790, USA; [email protected] (L.A.S.); [email protected] (S.N.) * Correspondence: [email protected] Abstract: Background: It is common for biopsies of concerning pulmonary nodules to result in cytologic “atypia” on biopsy, which may represent a benign response or a false negative finding. This investigation evaluated time to diagnosis and factors which may predict an ultimate diagnosis of lung cancer in these patients with atypia cytology on lung nodule biopsy. Methods: This retrospective study included patients of the Stony Brook Lung Cancer Evaluation Center who had a biopsy baseline diagnosis of atypia between 2010 and 2020 and were either diagnosed with cancer or remained disease free by the end of the observation period. Cox Proportional Hazard (CPH) Models were used to assess factor effects on outcomes. Results: Among 106 patients with an initial diagnosis of atypia, 80 (75%) were diagnosed with lung cancer. Of those, over three-quarters were diagnosed within 6 months. The CPH models indicated that PET positivity (SUV ≥ 2.5) (HR = 1.74 (1.03, 2.94)), nodule size > 3.5 cm (HR = 2.83, 95% CI (1.47, 5.45)) and the presence of mixed ground glass opacities (HR = 2.15 (1.05, 4.43)) significantly increased risk of lung cancer. Conclusion: Given the high conversion rate to Citation: Albano, D.; Santore, L.A.; cancer within 6 months, at least tight monitoring, if not repeat biopsy may be warranted during this Bilfinger, T.; Feraca, M.; Novotny, S.; time period for patients diagnosed with atypia. Nemesure, B. Clinical Implications of “Atypia” on Biopsy: Possible Keywords: atypia; lung cancer; lung nodule; PET; cytology Precursor to Lung Cancer? Curr. Oncol. 2021, 28, 2516–2522. https:// doi.org/10.3390/curroncol28040228 1. Introduction Received: 20 April 2021 Lung cancer incidence and mortality rates continue to rank among the highest of Accepted: 2 July 2021 Published: 6 July 2021 all cancer types in the United States [1]. Pulmonary nodule size and growth rate are known risk factors for lung cancer, [2] with nodules ≥ 8 mm posing a higher likelihood of malignancy [3]. Concerning scans typically warrant tissue sampling to assist with initial Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in diagnosis [4]. The most accessible sites are usually chosen for biopsy, [5] as different published maps and institutional affil- approaches carry different yields [6]. As it is not uncommon for tissue samples to be iations. classified as having atypical cellularity, repeat biopsies or surgical interventions are further recommended [7]. It remains unclear, however, how often a cytologic diagnosis of atypia is ultimately found to be a malignancy, and in what time frame this lung cancer diagnosis occurs. The purpose of this study was to evaluate the duration of time and potential risk factors associated with the development of lung cancer among patients with an initial Copyright: © 2021 by the authors. diagnosis of atypia. Licensee MDPI, Basel, Switzerland. This article is an open access article 2. Materials and Methods distributed under the terms and conditions of the Creative Commons This study retrospectively examined the electronic medical records (EMR) of all Attribution (CC BY) license (https:// patients seen by the Lung Cancer Evaluation Center (LCEC) at the Stony Brook Cancer creativecommons.org/licenses/by/ Center, Stony Brook, NY, USA, between 1 January 2010 and 31 May 2020. The LCEC was 4.0/). established to evaluate, diagnose, treat, and monitor patients found to have concerning Curr. Oncol. 2021, 28, 2516–2522. https://doi.org/10.3390/curroncol28040228 https://www.mdpi.com/journal/curroncol Curr. Oncol. 2021, 28, 2 Curr. Oncol. 2021, 28 2517 ter, Stony Brook, NY, USA, between 1 January 2010 and 31 May 2020. The LCEC was es- tablished to evaluate, diagnose, treat, and monitor patients found to have concerning pul- monary nodules. The LCEC maintains a database which captures longitudinal data for pulmonary nodules. The LCEC maintains a database which captures longitudinal data each patient, beginning with their baseline visit. The surveillance component of the pro- for each patient, beginning with their baseline visit. The surveillance component of the gram enables an opportunity to evaluate patients who span the full spectrum of disease program enables an opportunity to evaluate patients who span the full spectrum of disease andand includes includes those those who who are are diagnosed diagnosed with with ca cancerncer at at first first presentation, presentation, those those who who present present withwith benign benign nodules nodules and and develop develop cancer cancer over over time, time, and andthose those who whopresent present with withnon-ma- non- lignantmalignant lesions lesions yet remain yet remain cancer cancer-free-free while while under under care careof the of program. the program. UponUpon identification identification of of a asuspicious suspicious nodule nodule on on imaging, imaging, a aPET PET is is ordered ordered for for further further evaluation.evaluation. If Iffound found to to be be FDG FDG avid, avid, a abiopsy biopsy is isrecommended. recommended. A A biopsy biopsy that that yields yields atypia atypia isis presented presented at at the the weekly weekly tumor tumor board. board. Upon Upon consensus consensus of of the the multidisciplinary multidisciplinary care care team,team, which which includes includes representation representation from from all all program program sub sub-specialties,-specialties, an an individualized individualized patientpatient plan plan is is formulated. formulated. In In most most cases, cases, if ifthe the images images are are suspicious suspicious and and biopsy biopsy results results areare atypical, atypical, the the team team will will recommend recommend a arepeat repeat scan scan and and possible possible repeat repeat procedure procedure within within 1–1–66 months months [8] [8.]. DataData for for this this investigation, investigation, which which were were abstracted abstracted from from both both the the LCEC LCEC database database and and EMR,EMR, included included age, age, gender, gender, atypia status, datedate ofof atypiaatypia diagnosis, diagnosis, smoking smoking history history (current, (cur- rent,former, former, or never), or never), comorbidities comorbidities (history (history of diabetes, of diabetes, hypertension, hypertension, and emphysema), and emphy- family sema),history family of cancer, history and of nodulecancer, featuresand nodule including features lesion including size (in lesion cm), size mixed (in groundcm), mixed glass groundopacity glass type, opacity spiculation, type, locationspiculation, (upper location vs. lower (upper lobe, vs right. lower vs. lobe, left) right and PET vs. left) SUV. and PET PETpositivity SUV. PET was positivity defined as was PET defined SUV ≥ 2.5as PET [9,10 ].SU Additionally,V ≥ 2.5 [9,10] for. Additionally, those patients for who those were patiultimatelyents who diagnosed were ultimately with cancer, diagnosed the date with of cancercancer, diagnosis the date wasof cancer collected. diagnosis For patients was collected.who remained For patients disease-free who remained during thedisease observation-free during period, the observation the last date period, of examination the last datewas of recorded. examination was recorded. FigureFigure 11 presents presents the the inclusion inclusion and and exclusion exclusion crite criteriaria for for the the study study sample. sample. As As this this studystudy sought sought to to evaluate evaluate cytology cytology-proven-proven outcomes outcomes among among patients patients with with atypia, atypia, those those whowho did did not not have have a alung lung biopsy biopsy or or a adiagnosis diagnosis of of atypia atypia (n (n == 3007 3007)) were were excluded excluded from from thethe study, study, as as were were patients patients found found to to have have biopsy biopsy-confirmed-confirmed primary primary lung lung cancer cancer without without a aprevious previous diagnosis diagnosis of of atypia atypia (n (n == 1031 1031).). Among Among the the 143 143 patients patients receiving receiving a abaseline baseline diagnosisdiagnosis of of atypia, atypia, 4 4were were treated treated as as a aresult result of of a astrong strong clinical clinical suspicion suspicion of of lung lung cancer cancer despitedespite the the biopsy biopsy confirmatio confirmationn of of only only atypia atypia without without re re-biopsy,-biopsy, and and 1 1died died prior prior to to such such confirmation.confirmation. Those Those patients patients were were excluded excluded from from the the study study,, along along with with 32 32 others others who who did did notnot have have a aPET PET scan. scan. The The remaining remaining 106 106 patients patients represent represent the the basis basis for for this this investigation. investigation. FigureFigure 1. Inclusion 1. Inclusion and and exclusion
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