Impact of High-Grade Patterns in Early-Stage Lung Adenocarcinoma: A Multicentric Analysis.

OBJECTIVE: The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a significantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. METHODS: We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Differences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-high-grade and high-grade patterns. RESULTS: Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a significant better prognosis compared to T1a-b-c with high-grade pattern (p = 0.020), but the latter had similar OS compared to T2a (p = 0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a significantly better DFS compared to those with high-grade patterns (p = 0.034), and it was similar to T2a (p = 0.839). Multivariable analysis confirms the role of T descriptor according to high-grade pattern both for OS (p = 0.024; HR 1.285 95% CI 1.033-1.599) and DFS (p = 0.003; HR 1.196, 95% CI 1.054-1.344, respectively). These results were confirmed after the propensity score matching analysis. CONCLUSIONS: pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors.

Prognostic impact of lung adenocarcinoma second predominant pattern from a large European database.

BACKGROUND AND OBJECTIVES: Adenocarcinoma patterns could be grouped based on clinical behaviors: low- (lepidic), intermediate- (papillary or acinar), and high-grade (micropapillary and solid). We analyzed the impact of the second predominant pattern (SPP) on disease-free survival (DFS). METHODS: We retrospectively collected data of surgically resected stage I and II adenocarcinoma. SELECTION CRITERIA: anatomical resection with lymphadenectomy and pathological N0. Pure adenocarcinomas and mucinous subtypes were excluded. Recurrence rate and factors affecting DFS were analyzed according to the SPP focusing on intermediate-grade predominant pattern adenocarcinomas. RESULTS: Among 270 patients, 55% were male. The mean age was 68.3 years. SPP pattern appeared as follows: lepidic 43.0%, papillary 23.0%, solid 14.4%, acinar 11.9%, and micropapillary 7.8%. The recurrence rate was 21.5% and 5-year DFS was 71.1%. No difference in DFS was found according to SPP (p = .522). In patients with high-grade SPP, the percentage of SPP, age, and tumor size significantly influenced DFS (p = .016). In patients with lepidic SPP, size, male gender, and lymph-node sampling (p = .005; p = .014; p = .038, respectively) significantly influenced DFS. CONCLUSIONS: The impact of SPP on DFS is not homogeneous in a subset of patients with the intermediate-grade predominant patterns. The influence of high-grade SPP on DFS is related to its proportion in the tumor.

Minimally invasive treatment of diaphragmatic endometriosis: a 15-year single referral center's experience on 215 patients.

BACKGROUND: Diaphragmatic endometriosis (DE) is a rare and often misdiagnosed condition. Most of the times it is asymptomatic and due to the low accuracy of diagnostic tests, it is almost always detected during surgery for pelvic endometriosis. Its management is challenging and, until now, there are not guidelines about its treatment. METHODS: We describe a consecutive series of patients with DE managed by laparoscopy and videothoracoscopy (VATS) in our referral center in a period of 15 years. We developed a flow-chart classifying DE implants in foci, plaques and nodules and proposing an algorithm with the aim of standardizing the surgical approach. RESULTS: 215 patients were treated for DE. Lesions were almost always localized on the right hemidiaphragm (91%), and the endometriotic implants were distributed as: foci in 133 (62%), plaques in 24 (11%) and nodules in 58 patients (27%), respectively. In all cases of isolated pleural involvement, concomitant diaphragmatic hernia or lesions of the thoracic side of the diaphragm VATS was performed, alone or combined with laparoscopy, resulting in a total of 26 procedures. Following the proposed algorithm, specific surgical techniques were identified as the better approaches for the different types of the lesion, such as Argon Beam Coagulation and diathermocoagulation for diaphragmatic foci, peritoneal stripping for plaques, and nodulectomy or full-thickness resection of diaphragm for nodules. CONCLUSIONS: It is crucial to standardize the surgical approach of DE, according to the type of lesion, thus reducing the rate of under- or over-treatments and intra or postoperative complications. This kind of surgery should be performed in a Referral Center by a gynecologic surgeon with oncogynecologic expertise and skills, with the eventual support of a laparoscopic general surgeon, a specialized thoracic surgeon and a trained anesthesiologist.

Primary Hodgkin lymphoma of the lung arising with hemoptysis and pulmonary consolidation: a case report.

Classic Hodgkin lymphomas are neoplasms originating from lymphoid tissue. Primary extra-nodal classic Hodgkin lymphoma (PE-cHL) of the lung is rare. A 37-years-old Caucasian male was referred to our hospital for recurrent episodes of hemoptysis, cough and bronchitis. A computed tomography (CT) scan showed a massive left upper lung consolidation, which was positive at the positron emission tomography (PET) scan. After several inconclusive tests and no benefit from medical therapies, the patient underwent a left upper lobectomy; pathology report showed a classical type Hodgkin lymphoma with no lymph-nodes involvement. Four cycles of adjuvant chemotherapy were administered with no toxicity. At the last follow up 14 months after surgery, the patient is alive and free from disease. Primary extra-nodal classical Hodgkin lymphoma of the lung is a rare entity, but it should be considered as a differential diagnosis in young patients with pulmonary consolidation even without systemic symptoms.

Endometriosis Involving the Diaphragm: A Patient-Tailored Minimally Invasive Surgical Treatment.

BACKGROUND: Diaphragmatic endometriosis is a rare presentation of endometriosis and no standardized technique for surgical treatment is available so far. We aim to verify and describe feasibility, safety and post-operative outcomes of patients affected by diaphragmatic endometriosis treated with a minimally invasive video-assisted thoracic approach. METHODS: We prospectively collected data of all patients we operated on at our Institution for diaphragmatic endometriosis between 2015 and 2019. We included all patients with a previous histological diagnosis of pelvic or abdominal endometriosis who have complained chronic thoracic pain or who had two or more episodes of pneumothorax with or without radiological evidence of pleural and diaphragmatic endometriosis. RESULTS: During the study period, we operated on 22 patients, 20 on the right side, one on the left side and one bilaterally. Indication for surgery was based on symptoms and/or radiological evidence of diaphragmatic disease. Diaphragm was resected and reconstructed according to intraoperative findings; in 11 cases, an additional mesh was used to reinforce the suture. According to our experience with VATS, we shift from an open approach to a uniportal VATS technique. CONCLUSIONS: Surgery for diaphragmatic endometriosis can be safely performed using a minimally invasive VATS approach, which is feasible and safe even when more extensive diaphragmatic resections are required, and it allows a lower post-operative pain compared to the open approach. Moreover, uniportal VATS approach guarantees similar outcomes with better cosmetic results.

The everlasting issue of prolonged air leaks after lobectomy for non-small cell lung cancer: A data-driven prevention planning model in the era of minimally invasive approaches.

BACKGROUND AND OBJECTIVES: Prolonged air leaks (PAL) are the most frequent complication after lobectomy for non-small cell lung cancer, even in case of minimally invasive approaches. We developed a novel score to identify high-risk patients for PAL during minimally invasive lobectomy. METHODS: A dedicated database was created. We investigated preoperative candidate features and specific intraoperative variables. Univariate and subsequent logistic regression analysis with bootstrap resampling have been used. Model performance has been assessed by reckoning the area under the receiver operating characteristics curve and the Hosmer-Lemeshow goodness of fit. RESULTS: PAL (>5 days) occurred in 72 (15.69%) patients. Five variables emerged from the model. Each one was assigned a score to provide a cumulative scoring system: forced expiratory volume in 1 second below 86% (P = 0.004, 1.5 points), body mass index <24 ( P = 0.002, 1 point), active smoking ( P = 0.001, 1.5 points), incomplete fissures ( P = 0.004, 1.5 points), and adhesions ( P = 0.0001, 1 point). The new score provided a stratification into four risk classes. CONCLUSIONS: The risk score incorporates either general or more specific variables, providing a risk stratification that could be readily applied intra- and postoperatively. Henceforth, specific technical and management measures could be properly allocated to curb PAL.

Comparison of digital tomosynthesis and computed tomography for lung nodule detection in SOS screening program.

PURPOSE: To compare the lung nodules' detection of digital tomosynthesis (DTS) and computed tomography (CT) in the context of the SOS (Studio OSservazionale) prospective screening program for lung cancer detection. MATERIALS AND METHODS: One hundred and thirty-two of the 1843 subjects enrolled in the SOS study underwent CT because non-calcified nodules with diameters larger than 5 mm and/or multiple nodules were present in DTS. Two expert radiologists reviewed the exams classifying the nodules based on their radiological appearance and their dimension. LUNG-RADS classification was applied to compare receiver operator characteristics curve between CT and DTS with respect to final diagnosis. CT was used as gold standard. RESULTS: DTS and CT detected 208 and 179 nodules in the 132 subjects, respectively. Of these 208 nodules, 189 (91%) were solid, partially solid, and ground glass opacity. CT confirmed 140/189 (74%) of these nodules but found 4 nodules that were not detected by DTS. DTS and CT were concordant in 62% of the cases applying the 5-point LUNG-RADS scale. The concordance rose to 86% on a suspicious/non-suspicious binary scale. The areas under the curve in receiver operator characteristics were 0.89 (95% CI 0.83-0.94) and 0.80 (95% CI 0.72-0.89) for CT and DTS, respectively. The mean effective dose was 0.09 ± 0.04 mSv for DTS and 4.90 ± 1.20 mSv for CT. CONCLUSIONS: The use of a common classification for nodule detection in DTS and CT helps in comparing the two technologies. DTS detected and correctly classified 74% of the nodules seen by CT but lost 4 nodules identified by CT. Concordance between DTS and CT rose to 86% of the nodules when considering LUNG-RADS on a binary scale.

Ergon-trial: ergonomic evaluation of single-port access versus three-port access video-assisted thoracic surgery.

BACKGROUND: Single-port access video-assisted thoracic surgery (VATS), a technique progressively developed from the standard three-port approach in minimally invasive surgery, offers ergonomic advantages but also new challenges for the surgeon. We compared the ergonomics of three-port versus single-port VATS. METHODS: Posture analysis of surgeons was evaluated during 100 consecutive VATS wedge resections (50 triportal vs. 50 uniportal). Technically demanding procedures (major lung resection) were excluded. Operating table height, monitor height, distance and inclination were adjusted according to operator preference. Body posture was assessed by measuring head-trunk axial rotation and head flexion. Perceived physical strain was self-evaluated on the Borg Category Ratio (CR-10) scale. Mental workload was assessed with the National Aeronautics Space Administration-Task Load indeX (NASA-TLX), a multidimensional tool that rates workloads on six scales (mental, physical and temporal demand; effort; performance; frustration). RESULTS: All procedures were completed without complications. Head-trunk axial rotation was significantly reduced and neck flexion significantly improved in uniportal VATS. Viewing direction significantly declined (p = 0.01), body posture as measured on the Borg CR-10 scale was perceived as more stressful and the NASA-TLX score for overall workload was higher (p = 0.04) during triportal VATS. The NASA-TLX score for frustration was higher with uniportal VATS (p = 0.02), but the score for physical demand was higher in triportal VATS (p = 0.006). CONCLUSIONS: The surgeon can maintain a more neutral body posture during uniportal VATS by standing straight and facing the monitor with only minimal neck extension/rotation; however, frustration is greater than with triportal VATS.

Analysis of spontaneous pneumothorax in the city of Cuneo: environmental correlations with meteorological and air pollutant variables.

BACKGROUND AND PURPOSE: Primary spontaneous pneumothorax (PSP) tends to cluster. Previous studies have found a correlation between PSP and atmospheric pressure variations or thunderstorms. We conducted this study to analyze the PSP correlations with meteorological variables and the concentrations of air pollutants in the city of Cuneo in Italy (IT). METHODS: We evaluated prospectively 451 consecutive PSP patients treated between 2004 and 2010. For each day within the period analyzed, the meteorological parameters and pollutants data were recorded. Statistical analyses on PSP were done for distribution characteristics, spectral autocorrelation, and spectral analysis. Multivariate regression analyses were performed using artificial neural networks. RESULTS: Analysis of annual, seasonal, and monthly distributions showed no significant correlation between PSP and the time series. The spectral analysis showed that PSP events were not random. Correlations between meteorological and environmental variables confirmed that PSP was significantly more likely to occur on warm windy days with high atmospheric pressure and high mean nitrogen dioxide concentration. CONCLUSIONS: Meteorological parameters and atmospheric pollutants might explain the cluster onset of PSP.

The relationship between meteorological variations and the onset of spontaneous pneumothorax.

This is in reference to: Obuchi et al. (Surg Today 41(10):1380-1384, 2011).

Pathological and clinical features of multiple cancers and lung adenocarcinoma: a multicentre study.

OBJECTIVES: Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes. METHODS: We retrospectively reviewed data of patients radically operated on for stage I-II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups. RESULTS: We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008). CONCLUSIONS: In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern.

Prognostic role of standard uptake value according to pathologic features of lung adenocarcinoma.

OBJECTIVE: To evaluate the influence of lung adenocarcinoma second predominant pattern on the maximal standard uptake value (SUVmax) and its prognostic effect in different histologic groups. METHODS: We retrospectively collected surgically resected pathologic stage I and II lung adenocarcinoma from nine European institutions. Only patients who underwent preoperative PET-CT and with available information regarding SUVmax of T (SUVmaxT) and N1 (SUVmaxN1) component were included. RESULTS: We enrolled 344 patients with lung adenocarcinoma. SUVmaxT did not show any significant relation according to the second predominant pattern (p = 0.139); this relationship remained nonsignificant in patients with similar predominant pattern. SUVmaxT influenced the disease-free survival in the whole cohort (p = 0.002) and in low- and intermediate-grade predominant pattern groups (p = 0.040 and p = 0.008, respectively). In the high-grade predominant pattern cohort and in the pathologic N1 cases, SUVmaxT lost its prognostic power. SUVmaxN1 did not show any significant correlation with predominant and second predominant patterns and did not have any prognostic impact on DFS. CONCLUSIONS: SUVmaxT is influenced only by the adenocarcinoma predominant pattern, but not by second predominant pattern. Concurrently, in high-grade predominant pattern and pN1 group the prognostic power of SUVmaxT becomes nonsignificant.

Air leak and intraoperative bleeding in thoracic surgery: a Delphi consensus among the members of Italian society of thoracic surgery.

Background: Persistent air leak and the management of intraoperative blood loss are common threats in thoracic surgical practice. The availability of new procedures, technology and materials is constantly evolving topical hemostats and surgical sealants must be added to this toolkit. Topical hemostats and surgical sealants differ according to their chemical nature and physical characteristics, to their origin and mechanism of action, regulatory/registration and vigilance paths. A Delphi consensus was set to highlight the different points of view on the use of topical haemostatic products and sealants among the members of Italian Society of thoracic surgery. Methods: The board was formed by a group of five Italian experts; in the first phase after a careful review of the scientific literature and two rounds, the board finally generated 16 consensus statements for testing across a wider audience. During the second phase, the statements were collated into a questionnaire, which was electronically sent to a panel of 46 Italian surgeons, experts in the field. Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). Conclusions: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance.

Serratus plane block for video-assisted thoracoscopic surgery major lung resection: a randomized controlled trial.

OBJECTIVES: The aim of this study was to evaluate the impact of 2 different analgesic approaches on pain, postoperative rehabilitation exercises and rescue analgesics of 2 groups of patients undergoing video-assisted thoracoscopic surgery (VATS) major lung resection for cancer. METHODS: A total of 94 patients undergoing a VATS major lung resection were randomly allocated to 2 groups: the control group received intravenous and oral (i.e. systemic) analgesics while the intervention group received systemic analgesics plus pre-emptive serratus plane block. Pain perception was recorded until drainage removal or until 2 p.m. of postoperative day (POD) 3. In particular, the primary end point was defined as the peak pain perception on POD 1 (in the time frame between 6 a.m. and 2 p.m.). Secondary end points were the number of forced inspiration manoeuvers during rehabilitative incentive spirometry on POD 1 and 2 and the overall number of rescue analgesics requested by patients. RESULTS: Serratus plane block provided a better pain control between 6 a.m. and 2 p.m. of POD 1 (Numeric Rating Scale 1.7 vs 3.5; P < 0.001). Patients in the intervention group performed more forced inspiration manoeuvers at a mean higher volume during incentive spirometry (8.9 vs 7, P < 0.001, and 1010 vs 865 ml, P = 0.02). They required fewer rescue doses of analgesics (0.57 vs 1.1; P = 0.008). CONCLUSIONS: Serratus plane block provided a better pain control, entailing a better performance during postoperative rehabilitation exercises in terms of duration and quality of incentive spirometry. It diminished the patient's need for rescue analgesics during the early postoperative period. CLINICAL TRIAL REGISTRATION NUMBER: NCT03134729.

IgG4-related disease: a new challenging diagnosis mimicking lung cancer.

IgG4-related disease (IgG4-RD) is a progressive inflammatory disease that might rarely involve only the lungs. We retrospectively reviewed the preoperative, clinical and surgical features of patients with a pathology highly suggestive or probable diagnosis of IgG4-RD without extra-thoracic involvement. Five patients were selected, 2 were operated on the right side. Positron emission tomography-computed tomography (PET-CT) showed an uptake in all the patients (median 5.5), and 2 patients had an uptake at the thoracic lymph nodes. Two diagnoses were made through a CT-guided needle biopsy, while 3 were determined based on a lung wedge resection. The levels of serum IgG4 were elevated (>1.35 g/dl) in all the patients. Two patients had a highly suggestive diagnosis of IgG4-RD, and 3 patients had a probable diagnosis of IgG4-RD. The differential diagnosis between IgG4-RD and lung malignancies based only on radiological features is challenging and often requires histological confirmation. A careful preoperative workup and a multidisciplinary approach to PET-positive nodules might help to avoid unnecessary major lung resections.

Chest drain and thoracotomy for chest trauma.

Traumas are the leading cause of death in the first four decades of life. Nevertheless, thoracic traumas only seldom require invasive procedures. In particular, chest drain placement is required in case of pleural disruption causing haemothorax, pneumothorax or haemopneumothorax. Although large-bore chest drains have been traditionally used in case of haemothorax, recent evidences seem to question this routine, showing good performances of small-bore and pig tail drains. Although it is a common procedures, experience and training is needed to avoid complications which might be even lethal. Surgical exploration after thoracic trauma is rare, accounting for less than 3% of traumas. Penetrating traumas more likely require surgical exploration compared to blunt trauma. Anterolateral thoracotomy is usually performed in this setting, but also clamshell or hemi-clamshell approach can be used. In selected patients, minimally invasive techniques can be performed. Large randomized trials are still needed to assess and standardized the role of new tools and procedures in the thoracic trauma setting.

3q26 Amplification and polysomy of chromosome 3 in squamous cell lesions of the lung: a fluorescence in situ hybridization study.

PURPOSE: An overlapping area of gain at 3q26 has been reported in lung squamous cell carcinoma (SCC), but whether this also occurs in preneoplastic/preinvasive squamous cell proliferations and early-stage invasive carcinomas of the lung is still unknown. EXPERIMENTAL DESIGN: We evaluated the prevalence and the clinicopathologic implications of 3q26 amplification and polysomy of chromosome 3 in 31 preneoplastic/preinvasive squamous cell lesions of the bronchial mucosa and in 139 early-stage invasive pulmonary SCC, both of limited growth within the bronchial wall [early hilar SCC (EHSCC)] and involving the pulmonary parenchyma [parenchyma-infiltrating SCC (PISCC)]. Moreover, mRNA expression of two candidate genes (h-TERC and SKI-like), both mapping to the minimal common amplification region, was also studied by quantitative real-time reverse transcription-PCR. RESULTS: 3q26 amplification and polysomy of chromosome 3 were confined to malignant samples, with 37% of invasive SCC, and 27% of severe dysplasias/in situ carcinomas showing these chromosomal abnormalities. Amplification (with minimal common amplification region at 3q26.2), polysomy 3, concurrent amplification and polysomy 3, or other changes (monosomy) were found in 25 SCC and 1 dysplasia, 24 and 2, 2 and 0, and 1 and 0, respectively. Amplification was significantly associated with EHSCC, polysomy 3 with PISCC. 3q26 amplification correlated with increased tumor diameter and a history of smoking, whereas polysomy 3 correlated with tumor diameter, pT class, and p53, p21, and fascin immunoreactivity. No relationship of either 3q26 gain or polysomy was found with patients' survival. Overexpression of h-TERC or SKI-like mRNA was found in 3q26-amplified or polysomic SCC, with higher levels of h-TERC in the former and of SKI-like in the latter. CONCLUSIONS: 3q26 amplification and chromosome 3 polysomy may be related to the development of invasive SCC, with differential distribution in tumor subsets, despite substantial histologic uniformity. Both h-TERC and SKI-like may be involved in tumor progression.

Correction: PD-L1 expression heterogeneity in non-small cell lung cancer: evaluation of small biopsies reliability.

[This corrects the article DOI: 10.18632/oncotarget.21485.].

PD-L1 Expression Heterogeneity in Non-Small Cell Lung Cancer: Defining Criteria for Harmonization between Biopsy Specimens and Whole Sections.

INTRODUCTION: Determination of programmed death ligand 1 (PD-L1) expression defines eligibility for treatment with pembrolizumab in patients with advanced NSCLC. This study was designed to better define which value across core biopsy specimens from the same case more closely reflects the PD-L1 expression status on whole sections and how many core biopsy specimens are needed for confident classification of tumors in terms of PD-L1 expression. METHODS: We built tissue microarrays as surrogates of biopsies collecting five cores per case from 268 cases and compared PD-L1 staining results obtained by using the validated clone SP263 with the results obtained by using whole tumor sections. RESULTS: We found an overall positivity in 39% of cases at a cutoff of 1% and in 10% of cases at a cutoff of 50%. The maximum value across cores was associated with high concordance between cores and whole sections and the lowest number of false-negative cases overall. To reach high concordance with whole sections, four and three cores are necessary at cutoffs of 1% and 50%, respectively. Importantly, with 20% as the cutoff for core biopsy specimens, fewer than three cores showed high sensitivity and specificity in identifying cases with 50% or more of tumor cells positive for PD-L1 on whole sections. Specifically, for PD-L1 expression values of 20% to 49% on cores, the probabilities of a tumor specimen expressing PD-L1 in at least 50% of cells on a whole section were 46% and 24% with one and two biopsy specimens, respectively. CONCLUSIONS: An accurate definition of the criteria to determine the PD-L1 status of a given tumor may greatly help in selecting those patients who could benefit from anti-programmed cell death 1/PD-L1 treatment.