PCCM Reports — Pulmonary and Critical Care Medicine; Henry Ford Medical Group

Original research Interventional Pulmonology

The Association of Reactive Mediastinal and Hilar Lymphadenopathies with Congestive Heart Failure

Alaa Abu Sayf, MD1; Michael Reaume, MD1; Vincent Lipari, MD2; Bruno DiGiovine, MD3; Michael Simoff, MD1; Javier Diaz-Mendoza, MD1

1 Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital, Detroit, Michigan

2 Division of Cardiology, Ascension St John, Detroit, Michigan

3 IHA Pulmonary, Critical Care and Sleep Medicine, St Joseph Mercy, Ann Arbor, Michigan

PCCM Reports · 2026 · Volume 1 · Interventional Pulmonology

Abstract

Background. Isolated mediastinal and hilar lymphadenopathy (MLAD) is a common imaging finding, often leading to tissue sampling to achieve a diagnosis. Patients with congestive heart failure (CHF) are likely to have 'reactive lymphadenopathy' in this setting and therefore not yield an alternative etiology. Our study aimed to identify risk factors in patients with isolated MLAD that may aid in predicting a diagnosis of reactive lymphadenopathy, particularly those with underlying CHF.

Methods. Retrospective review and 12-month follow-up of all patients who underwent EBUS-TBNA bronchoscopy between June 1, 2010 and December 31, 2015 at a single institution.

Results. Of 1773 patients who underwent EBUS-TBNA, 46 had isolated MLAD. The most common diagnoses were reactive lymphadenopathy (23/46 [50%]), granulomatous disease (22/46 [47.8%]), and malignancy (1/46 [2.2%]). Of the 23 patients with reactive lymphadenopathy, 21 had CHF (21/23 [91.3%]). Accordingly, of the 24 patients with CHF, 21 (87%) had reactive lymphadenopathy versus 3 (13%) having an alternative diagnosis (p < 0.01). On a univariate analysis, patients with isolated MLAD and CHF were 70 times more likely to have reactive lymphadenopathy (OR 70 [10.56-463.86], p <0.001). On multivariate analysis, CHF was the only factor predictive of a diagnosis of reactive lymphadenopathy (OR 47.2 [6.68 – 333.59], p < 0.001).

Conclusions. There is a strong association between CHF and a diagnosis of reactive MLAD in the setting of radiographically isolated MLAD. Clinicians should be alert to these associations to balance the known procedural risks of EBUS-TBNA with the benefits of finding an unlikely alternative diagnosis.

Keywords: Adenopathy, bronchoscopy, congestive heart failure

1. Introduction

Mediastinal lymphadenopathy (MLAD) is a frequently described incidental finding on chest imaging.[1, 2] This finding can be seen in the setting of a broad range of diagnoses, including, but not limited to congestive heart failure (CHF), pulmonary hypertension (PH), malignancy, infections, and granulomatous diseases.[3-6] Patients with MLAD may undergo tissue sampling to achieve a diagnosis. Tissue sampling is commonly done via endobronchial ultrasound guided transbronchial fine needle aspiration (EBUS-TBNA), which is a safe, accurate, and cost-effective modality in the workup of MLAD.[7-10] It has become the procedure of choice in the initial investigation of mediastinal and hilar lymphadenopathies.[11]

Patients with CHF commonly have MLAD,[3, 12-15] and it is often isolated MLAD (adenopathy with no or minimal parenchymal lung abnormalities). In these cases, tissue sampling in the absence of other pathology will reveal reactive lymphadenopathy (i.e. enlarged lymph nodes as a reaction to their underlying diagnosis of CHF).[5] Because performing an EBUS-TBNA on these patients would not be advantageous,[3] it is important to carefully consider which subset patients with MLAD are likely to benefit from undergoing tissue sampling. While EBUS-TBNA is generally well tolerated, it is not without risks, including the adverse effects of sedation, bleeding, infection, and less commonly pneumothorax.[8-10, 16] In this study, we aimed to identify risk factors in patients with isolated MLAD that may aid in the assessment of a diagnosis of reactive lymphadenopathy, particularly those with an underlying diagnosis of CHF. This could potentially obviate the need for bronchoscopies in a subset of patients with isolated MLAD.

2. Methods

We performed a retrospective review of all patients who underwent EBUS-TBNA bronchoscopy between June 1, 2010 and December 31, 2015 at a single institution. The first screening of this population of patients was designed to select those with radiographically isolated MLAD. This was done by physicians blinded to the final pathologic diagnosis, by reviewing the most recent CT chest report prior to the procedure date – patients were only included if they had a CT chest within 30 days prior to the bronchoscopy. Radiographically isolated MLAD was defined as MLAD in the absence of any of the following: a lung nodule > 1cm, lung mass (> 3cm), mediastinal mass (> 3cm), diffuse parenchymal lung disease (not including emphysema, bronchiectasis, or findings suggestive of decompensated CHF such as central ground glass and pleural effusions), or extrathoracic adenopathy. The second screening was performed by a second reviewer, also blinded to the final pathological diagnosis, who reviewed the medical record to exclude patients with any history of lung cancer, other malignancy within the last 5 years, or previous diagnosis of sarcoidosis. Of the remaining patients, the demographics of age, gender, and race were collected.

The remaining subjects were then classified into two groups: subjects with CHF, and subjects classified as having no-CHF. A diagnosis of CHF was defined in this study as either: 1) an echocardiogram within 6 months prior to the procedure showing one or more of the following: ejection fraction < 45%, diastolic dysfunction with impaired relaxation grade III – IV, right atrial pressure >10 mm Hg, dilated right ventricle; or 2) a clinical diagnosis of CHF documented in the medical records.

All EBUS-TBNA bronchoscopies were performed by one of three formally trained interventional pulmonology specialists. Prior to the procedure, the patient images were independently reviewed by the interventional pulmonologist. This step acted as a final screening to confirm the presence or absence of radiographically isolated MLAD. Radiologic size of the lymph nodes on CT was based on the shortest axial diameter measured using the Picture Archiving and Communication System (PACS). During EBUS-TBNA bronchoscopy, the location and nomenclature of thoracic lymphadenopathy was based on the Mountain and Dresler lymph node classification.[17] Lymph node sampling was based on size and accessibility by the operator and was left entirely to their discretion. All lymph nodes greater than 5mm are typically sampled. Lymph node samples were collected and sent for cytologic evaluation. For our analysis, biopsy results of all the lymph node samples were reviewed and separated into different categories: 1) Target organ not sampled, 2) Granulomatous inflammation, 3) Malignancy (of any type), and 4) Presence of normal Lymphocytes. There is standard language adapted for communication between the interventional pulmonologist and pathology to indicate adequate target organ sampling. Patients were followed up 12 months after bronchoscopy to look for alternative diagnosis for MLAD – this was done via review of the medical record (office visits and radiology reports). The definition of “Reactive lymphadenopathy” was made if sample showed “presence of normal lymphocytes”, and a subsequent 12-month follow-up did not reveal an alternative diagnosis.

Statistical analysis

All analyses were performed with STATA software, version 12.0 (Stata Corp, College Station, TX USA). Continuous variables were compared using the Student’s t-test or the Kruskal–Wallis rank-sum test in cases of non-normally distributed variables and expressed, respectively, as means and standard deviation (SD) or median and interquartile range [IQR]. Categorical variables were expressed as percentages and analyzed using a chi-square test.

To determine independent risk factors for a diagnosis of reactive lymphadenopathy, univariate logistic regression was used to test for the following factors: age, race, gender, maximum node size, number of nodes sampled and presence of CHF. All variables with p < 0.10 were kept in the model and included in multivariate analysis (adjusted odds ratio).

3. Results

Of 1,773 patients who underwent EBUS-TBNA at Henry Ford Hospital during the study period, 1,727 were excluded, leaving 46 patients (24 with CHF and 22 without). Exclusions were due to insufficient data, lung or mediastinal masses, lung nodules, extrathoracic lymphadenopathy, or recent malignancy. The most common reasons were lung mass (n = 639) and mediastinal mass (n = 454). Baseline characteristics did not differ by CHF status (Table 1). Patients with or without CHF had a similar distribution of mediastinal and hilar adenopathy, although fewer CHF patients had enlarged lymph nodes in station 4R (14/24 [58.3%] vs 19/22 [86.4%] respectively, p = 0.035) and 11Rs (10/24 [41.7%] vs 16/22 [72.7%] respectively, p = 0.034).

Biopsy results of the 46 patients with isolated MLAD are shown in Table 2. All lymph node aspirations were adequate samples of lymphoid tissue. The most common diagnosis was reactive lymphadenopathy (23/46 [50%]), followed by granulomatous disease (22/46 [47.8%]), and malignancy (1/46 [2.2%]). Of the 23 patients with reactive lymphadenopathy, 21 of them had CHF (21/23 [91.3%]). Accordingly, of the 24 patients with CHF, 21 (87%) had reactive lymphadenopathy versus only 3 (13%) having non-reactive lymph nodes (p < 0.01). None of the patients with reactive lymphadenopathy had an alternative diagnosis after 12-month follow up. All biopsy results with granulomatous disease were “noncaseating”, and these patients were all treated for sarcoidosis.

On a univariate analysis (Table 3), patients with isolated MLAD who had a diagnosis of CHF were 70 times more likely to have reactive lymphadenopathy (OR 70 [10.56-463.86], p <0.001). This finding occurred in 21/24 [87.5%] patients in this group (isolated MLAD with CHF). Accordingly, those same patients were less likely to have an alternative diagnosis (OR 0.006 [0.001-0.71], p <0.001). Age was also predictive of a diagnosis of reactive lymphadenopathy (OR 1.09 [1.03 – 1.16], p 0.003). Maximum lymph node diameter, gender, race, and number of nodes samples did not correlate with a reactive lymphadenopathy diagnosis. On multivariate analysis (Table 3), CHF was the only factor that remained predictive of a diagnosis of reactive lymphadenopathy (OR 47.2 [6.68 – 333.59], p < 0.001).

Table 1. Baseline characteristics

—No CHF n=22CHF n=24p
Age4661.8< 0.001
Male, n (%)13 (59)13 (54)0.74
Race
African American9 (41)9 (37.5)0.81
Maximum node size, mm (median [IQR])18.4 (12.8-22.9)15.85 (12.65-21.55)0.55
Nodes sampled, n (SD)3.27 (0.98)2.54 (1.21)0.03
Enlarged, n (%)
Mediastinal20 (51.3)19 (48.7)0.27
2R1 (4.6)5 (20.8)0.10
4R19 (86.4)14 (58.3)0.04
4L7 (31.8)6 (25)0.61
Hilar21 (50)21 (50)0.34
721 (95.5)19 (79.2)0.10
10R0 (0)1 (4.2)0.33
10L0 (0)0 (0)--
11Rs16 (72.7)10 (41.7)0.03
11L7 (31.8)5 (20.8)0.40
12R1 (4.6)1 (4.2)0.95

Table 2. Pathologic Diagnosis

DiagnosisNo CHF (22)CHF (24)Total (46)
Malignancy0111
Granulomatous disease20222
Reactive Lymphadenopathy22123

1 Lymphoma

Table 3. Predictors of a Diagnosis of Reactive Lymphadenopathy

—Unadjusted Odds Ratio (95% CI)p
CHF70 (10.56-463.86)<0.001
Age1.09 (1.03-1.16)0.003
Gender1 (0.31-3.21)1.00
Race1.44 (0.44-4.74)0.55
Nodes sampled0.85 (0.51-1.40)0.53
Maximum LN diameter0.96 (0.87-1.05)0.37
Adjusted Odds Ratio (95% CI)
CHF47.2 (6.68-333.59)<0.001
Age1.04 (0.97-1.12)0.29

4. Discussion

Our study shows that patients with radiographic findings of isolated MLAD are likely to have a non-malignant diagnosis. In addition, patients with a diagnosis of CHF have a 47-fold increased likelihood of having reactive lymphadenopathy. This association is similar to the study by Evison, in which reactive lymphadenopathy occurred in all 13 of their patients with CHF.[5] It is imperative that clinicians carefully consider this association when performing EBUS-TBNA to balance the known procedural risks versus the potential benefit of finding an unlikely alternative diagnosis.

Prior studies support a strong association between CHF and the presence of MLAD.[3, 12-15] The pathophysiology of this phenomenon being first described in 1967 by Leeds et al.[18] Leeds found that the capability of the lymphatic system to expand allowed for the removal of fluids in the pulmonary interstitium and venous circulation in states of acute and chronic heart failure.[18] When treated, the lymphadenopathy tends to improve or resolve.[13, 19, 20] If we consider that an estimated 6.2 million adults in the United States have heart failure[21] – the prevalence of which is anticipated to increase over time to more than 8 million in 2030[22] – it is evident that this imaging finding can lead to an immense number of biopsies nationwide that are unlikely to add useful clinical information. An approach with aggressive treatment of the underlying cause and serial imaging may avoid unnecessary procedures.

Our study strengths include the large population from which our study cohort was extracted, with over 1700 patients in a 5-year period. Furthermore, our methods are congruent the standard clinical practice when assessing patient images, with independent review of the radiology report by a first “screening” (typically the referring physician in usual clinical practice), followed by independent review of the images by the physician performing the procedure (in our case, a highly experienced bronchoscopist from the interventional pulmonology group). Thus, our methods not only are reproducible but reflect a ‘usual’ clinical approach to mediastinal and hilar lymphadenopathy. Additionally, we noted clear trends supporting our hypothesis that patients with CHF and isolated MLAD are likely to have reactive lymphadenopathy on biopsy. Furthermore, we clearly defined both CHF and MLAD in our population, making our study methods precise and reproducible. Conversely, our study is limited by the single center design – patients referred to our center for bronchoscopic evaluation may differ from those at other centers, limiting external validity. In addition, the technique and biopsy approach in our population was not protocolized (timing of biopsy, lymph nodes sampled, etc.) which may not reflect the approach of other providers faced with the same clinical situation. Nonetheless, our study is relevant to providers referring for, or performing EBUS-TBNA. Our evaluation of patients with and without CHF undergoing tissue sampling for isolated MLAD has not been directly explored previously in the literature.

In conclusion, there is a strong association between a clinical diagnosis of CHF and a diagnosis of reactive MLAD in the setting of radiographically isolated MLAD. Clinicians should be alert to these associations to carefully balance the known procedural risks of EBUS-TBNA with the benefits of finding an unlikely alternative diagnosis. Prospective, multicenter studies performed on CHF patients could provide better understanding of the phenomenon of reactive MLAD.

Declarations

Conflicts of Interest and Funding

Alaa Abu Sayf, Michael Reaume, Vincent Lipari, Bruno DiGiovine, Michael Simoff, and Javier Diaz-Mendoza have no relevant conflicts of interest to disclose. There are no funding sources to report.

Prior presentation

This study was presented at the American Thoracic Society international conference in San Diego, California on May 22, 2018

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Corresponding author: Javier Diaz-Mendoza, MD; 313-916-2600; jdiaz1@hfhs.org.
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