Nonspecific Pleuritis: Optimal Duration of Follow-Up Zachary S. DePew, MD, Akash Verma, MRCP, Dennis Wigle, MD, PhD, John J. Mullon, MD, Francis C. Nichols, MD, and Fabien Maldonado, MD Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota
Background. Nonspecific pleuritis (NSP) is a frequent diagnosis after parietal pleural biopsy, but the clinical significance of this finding and need for further follow-up have not been firmly established. Previous reports suggest that 5% to 25% of patients with NSP are subsequently diagnosed with pleural malignancy. Methods. Our pathology database was queried for patients with histologic evidence of NSP from January 01, 2001, to December 31, 2012 (n [ 413). Patients with less than 1 year of follow-up after biopsy, diagnosis of empyema, tuberculous pleuritis, active systemic connective tissue disease or vasculitis, or active malignancy were excluded (n [ 327). The remaining patients were included and their medical records were reviewed. Results. Eighty-six patients were included. Mean follow up was 1,824 ± 1,032 days (range, 409 to 4,599 days). Three of the 86 patients with NSP (3.5%) were subsequently
diagnosed with pleural malignancy. All 3 patients were found to have mesothelioma with a mean time from biopsies to diagnosis of 205 ± 126 days (range, 64 to 306 days). Twenty-two of 86 patients (25.5%) had a possible identifiable cause of pleural inflammation (benign disease). After exclusion of these 22 patients, the incidence of malignancy was 3 of 64 (4.7%). Conclusions. The incidence of subsequent pleural malignancy (mesothelioma) among patients found to have NSP based on pleural biopsy was 3.5%. Occult mesothelioma in patients with NSP will most likely be diagnosed within 1 year of the initial pleural biopsy; therefore, these patients should be followed for a minimum of 1 year to allow for timely detection of occult pleural malignancy.
T
varies from 6 months to 4 years [12–15]. Clinical surveillance of patients diagnosed with NSP appears warranted; however, there is no current consensus on the appropriate clinical evaluation and follow-up for these patients. We conducted this study to determine the incidence of subsequent pleural malignancy among patients diagnosed with NSP at Mayo Clinic by multiple diagnostic methods, and to attempt to determine the appropriate follow-up time for patients diagnosed with NSP.
echniques for the diagnostic evaluation of pleural diseases in order of invasiveness include thoracentesis, closed pleural biopsy, image-guided biopsies (ultrasound or computed tomography [CT]), medical thoracoscopy, video-assisted thoracoscopic surgery (VATS), and thoracotomy. Of these, thoracoscopic techniques and thoracotomy provide the highest overall diagnostic yields, in the range of 80% to 98% [1–3]. However, anywhere from 9% to 50% of these cases diagnosed with parietal pleural biopsy consist of nonspecific acute or chronic pleuritis, the implications of which are unclear [4–13]. Such cases are commonly reported as “nonspecific pleuritis” (NSP), “fibrinous pleuritis,” or “idiopathic pleuritis.” The finding of NSP is sometimes challenging for the provider because of ongoing uncertainty about the possibility of a falsenegative result from sampling error. Published data suggest that as many as 5% to 25.5% of these patients will subsequently be diagnosed with pleural malignancy, the most common of which is mesothelioma in 2.5% to 15.8% of cases [12, 14–21]. These studies have a wide range of follow-up extending anywhere from 6 months to 15 years. The reported time from the diagnosis of NSP to subsequent diagnosis of mesothelioma in previous studies Accepted for publication Jan 28, 2014. Address correspondence to Dr Maldonado, Mayo Clinic, Division of Pulmonary and Critical Care Medicine, 200 First St SW, Rochester, MN 55905; e-mail: [email protected].
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2014;-:-–-) Ó 2014 by The Society of Thoracic Surgeons
Patients and Methods This study was approved by the Institutional Review Board of the Mayo Clinic College of Medicine (IRB No. 12-010183). Our pathology database was queried for all cases of parietal pleural biopsy resulting in a histologic diagnosis of NSP (any combination of acute or chronic inflammation with or without fibrosis) from January 01, 2001, to December 31, 2012, yielding 413 cases. The electronic medical records of each patient were retrospectively reviewed by 2 independent reviewers (Z.S.D., F.M.). Patients with less than 1 year of clinical follow-up after the biopsy or with a known or probable cause for the pleuritis including empyema, tuberculous pleuritis, active systemic vasculitis, or active malignancy were excluded (n ¼ 327). The remaining 86 patients were included in the study. All included patients had at least one clinical encounter with a physician a minimum of 1 year after 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.01.057
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DEPEW ET AL NONSPECIFIC PLEURITIS FOLLOW-UP DURATION
their initial pleural biopsy. Their medical records were reviewed with extraction of data including demographics, operative details, length of clinical follow-up, subsequent pleural pathology results, and suspected clinical diagnoses. Patients without documentation of subsequent pleural malignancy at or preceding their most recent follow-up were assumed to have had NSP without occult pleural malignancy. Qualitative data are presented as percentages, and quantitative data, as mean standard deviation.
Procedural Methodology All included patients underwent a diagnostic operation with or without the assistance of medical trainees (house officers) under the direct supervision of an attending surgeon. Given the variability in both the types of procedures and the specialists performing them represented in this study, there was no standardized operative protocol regarding the sequence of biopsies. A generally adopted approach was to complete a thorough inspection of the parietal pleura before biopsying any obvious abnormalities. If no abnormalities were noted, biopsy specimens were acquired from multiple sites at random. When encountered, benign-appearing asbestos plaques were avoided with selective sampling of the surrounding pleura. Intraoperative frozen sectioning was generally used to determine whether sufficient diagnostic material had been acquired. If frozen sectioning did not reveal evidence of diagnostic material, larger additional samples were acquired.
Results Summary of Patients With Nonspecific Pleuritis A total of 86 patients were included in our analysis. Patient characteristics are listed in Table 1. Average age was 66.3 16.1 years with a slight male predominance (59.3%). Mean follow-up was 1,824 1,032 days (range, 409 to 4,599 days). After consensus review by 2 of the authors (Z.S.D., F.M.), 22 patients (25.5%) had a possible identifiable cause of pleural inflammation (benign disease). We therefore distinguish in our analyses NSP (n ¼ 86) from idiopathic NSP (n ¼ 64) and present both data analyses separately. These 22 patients included those with a history of sternotomy or thoracotomy within 12 months preceding the pleural biopsy (n ¼ 11; 12.8%), history of autoimmune disease (n ¼ 6; 7%), or a possible diagnosis of parapneumonic effusion (n ¼ 5; 5.8%; Fig 1). Overall, 3 of 86 patients with NSP (3.5%) were subsequently diagnosed with pleural malignancy. All 3 patients were found to have mesothelioma with a mean time from biopsies to diagnosis of 205 126 days (range, 64 to 306 days). After exclusion of patients with a potentially attributable benign cause, ie, idiopathic NSP, the incidence of malignancy was 3 of 64 patients (4.7%). Procedural details are listed in Table 2. The most common indication for pleural biopsy was a persistent pleural effusion (n ¼ 63; 73.3%), with the remaining indications including pneumothorax (n ¼ 6; 7%), an
Ann Thorac Surg 2014;-:-–-
Table 1. Patient Detailsa Patient Details Age (y) Sex Male Female Tobacco use (pack-years) 0 1–20 21–50 >50 Follow up duration (days) Diagnosis of pleural malignancy during follow-up Mesothelioma Time from NSP biopsy to cancer diagnosis (days) Possible etiology of NSP Sternotomy or thoracotomy
Background. Nonspecific pleuritis (NSP) is a frequent diagnosis after parietal pleural biopsy, but the clinical significance of this finding and need for further follow-up have not been firmly established. Previous reports suggest that 5% to 25% of patients with NSP are subsequently diagnosed with pleural malignancy. Methods. Our pathology database was queried for patients with histologic evidence of NSP from January 01, 2001, to December 31, 2012 (n [ 413). Patients with less than 1 year of follow-up after biopsy, diagnosis of empyema, tuberculous pleuritis, active systemic connective tissue disease or vasculitis, or active malignancy were excluded (n [ 327). The remaining patients were included and their medical records were reviewed. Results. Eighty-six patients were included. Mean follow up was 1,824 ± 1,032 days (range, 409 to 4,599 days). Three of the 86 patients with NSP (3.5%) were subsequently
diagnosed with pleural malignancy. All 3 patients were found to have mesothelioma with a mean time from biopsies to diagnosis of 205 ± 126 days (range, 64 to 306 days). Twenty-two of 86 patients (25.5%) had a possible identifiable cause of pleural inflammation (benign disease). After exclusion of these 22 patients, the incidence of malignancy was 3 of 64 (4.7%). Conclusions. The incidence of subsequent pleural malignancy (mesothelioma) among patients found to have NSP based on pleural biopsy was 3.5%. Occult mesothelioma in patients with NSP will most likely be diagnosed within 1 year of the initial pleural biopsy; therefore, these patients should be followed for a minimum of 1 year to allow for timely detection of occult pleural malignancy.
T
varies from 6 months to 4 years [12–15]. Clinical surveillance of patients diagnosed with NSP appears warranted; however, there is no current consensus on the appropriate clinical evaluation and follow-up for these patients. We conducted this study to determine the incidence of subsequent pleural malignancy among patients diagnosed with NSP at Mayo Clinic by multiple diagnostic methods, and to attempt to determine the appropriate follow-up time for patients diagnosed with NSP.
echniques for the diagnostic evaluation of pleural diseases in order of invasiveness include thoracentesis, closed pleural biopsy, image-guided biopsies (ultrasound or computed tomography [CT]), medical thoracoscopy, video-assisted thoracoscopic surgery (VATS), and thoracotomy. Of these, thoracoscopic techniques and thoracotomy provide the highest overall diagnostic yields, in the range of 80% to 98% [1–3]. However, anywhere from 9% to 50% of these cases diagnosed with parietal pleural biopsy consist of nonspecific acute or chronic pleuritis, the implications of which are unclear [4–13]. Such cases are commonly reported as “nonspecific pleuritis” (NSP), “fibrinous pleuritis,” or “idiopathic pleuritis.” The finding of NSP is sometimes challenging for the provider because of ongoing uncertainty about the possibility of a falsenegative result from sampling error. Published data suggest that as many as 5% to 25.5% of these patients will subsequently be diagnosed with pleural malignancy, the most common of which is mesothelioma in 2.5% to 15.8% of cases [12, 14–21]. These studies have a wide range of follow-up extending anywhere from 6 months to 15 years. The reported time from the diagnosis of NSP to subsequent diagnosis of mesothelioma in previous studies Accepted for publication Jan 28, 2014. Address correspondence to Dr Maldonado, Mayo Clinic, Division of Pulmonary and Critical Care Medicine, 200 First St SW, Rochester, MN 55905; e-mail: [email protected].
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2014;-:-–-) Ó 2014 by The Society of Thoracic Surgeons
Patients and Methods This study was approved by the Institutional Review Board of the Mayo Clinic College of Medicine (IRB No. 12-010183). Our pathology database was queried for all cases of parietal pleural biopsy resulting in a histologic diagnosis of NSP (any combination of acute or chronic inflammation with or without fibrosis) from January 01, 2001, to December 31, 2012, yielding 413 cases. The electronic medical records of each patient were retrospectively reviewed by 2 independent reviewers (Z.S.D., F.M.). Patients with less than 1 year of clinical follow-up after the biopsy or with a known or probable cause for the pleuritis including empyema, tuberculous pleuritis, active systemic vasculitis, or active malignancy were excluded (n ¼ 327). The remaining 86 patients were included in the study. All included patients had at least one clinical encounter with a physician a minimum of 1 year after 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.01.057
2
DEPEW ET AL NONSPECIFIC PLEURITIS FOLLOW-UP DURATION
their initial pleural biopsy. Their medical records were reviewed with extraction of data including demographics, operative details, length of clinical follow-up, subsequent pleural pathology results, and suspected clinical diagnoses. Patients without documentation of subsequent pleural malignancy at or preceding their most recent follow-up were assumed to have had NSP without occult pleural malignancy. Qualitative data are presented as percentages, and quantitative data, as mean standard deviation.
Procedural Methodology All included patients underwent a diagnostic operation with or without the assistance of medical trainees (house officers) under the direct supervision of an attending surgeon. Given the variability in both the types of procedures and the specialists performing them represented in this study, there was no standardized operative protocol regarding the sequence of biopsies. A generally adopted approach was to complete a thorough inspection of the parietal pleura before biopsying any obvious abnormalities. If no abnormalities were noted, biopsy specimens were acquired from multiple sites at random. When encountered, benign-appearing asbestos plaques were avoided with selective sampling of the surrounding pleura. Intraoperative frozen sectioning was generally used to determine whether sufficient diagnostic material had been acquired. If frozen sectioning did not reveal evidence of diagnostic material, larger additional samples were acquired.
Results Summary of Patients With Nonspecific Pleuritis A total of 86 patients were included in our analysis. Patient characteristics are listed in Table 1. Average age was 66.3 16.1 years with a slight male predominance (59.3%). Mean follow-up was 1,824 1,032 days (range, 409 to 4,599 days). After consensus review by 2 of the authors (Z.S.D., F.M.), 22 patients (25.5%) had a possible identifiable cause of pleural inflammation (benign disease). We therefore distinguish in our analyses NSP (n ¼ 86) from idiopathic NSP (n ¼ 64) and present both data analyses separately. These 22 patients included those with a history of sternotomy or thoracotomy within 12 months preceding the pleural biopsy (n ¼ 11; 12.8%), history of autoimmune disease (n ¼ 6; 7%), or a possible diagnosis of parapneumonic effusion (n ¼ 5; 5.8%; Fig 1). Overall, 3 of 86 patients with NSP (3.5%) were subsequently diagnosed with pleural malignancy. All 3 patients were found to have mesothelioma with a mean time from biopsies to diagnosis of 205 126 days (range, 64 to 306 days). After exclusion of patients with a potentially attributable benign cause, ie, idiopathic NSP, the incidence of malignancy was 3 of 64 patients (4.7%). Procedural details are listed in Table 2. The most common indication for pleural biopsy was a persistent pleural effusion (n ¼ 63; 73.3%), with the remaining indications including pneumothorax (n ¼ 6; 7%), an
Ann Thorac Surg 2014;-:-–-
Table 1. Patient Detailsa Patient Details Age (y) Sex Male Female Tobacco use (pack-years) 0 1–20 21–50 >50 Follow up duration (days) Diagnosis of pleural malignancy during follow-up Mesothelioma Time from NSP biopsy to cancer diagnosis (days) Possible etiology of NSP Sternotomy or thoracotomy
