Sarcoidal reactions in regional lymph nodes of patients with non-small cell lung cancer: Incidence and implications for minimally invasive staging with endobronchial ultrasound

doi:10.1016/j.lungcan.2009.03.001

Lung Cancer

Volume 66, Issue 3, December 2009, Pages 305-308

https://doi.org/10.1016/j.lungcan.2009.03.001 Get rights and content

Abstract

Background

Both malignancy and granulomatous diseases may be diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Sarcoidal reactions may be seen in the presence of non-small cell lung cancer (NSCLC). Demonstration of granulomas by lymph node EBUS-TBNA in the staging of NSCLC is of uncertain significance.

Aims

To determine the frequency of sarcoidal reactions in lymph nodes of patients with NSCLC. To report the frequency of co-involvement of sarcoidal reactions with metastatic NSCLC in regional lymph nodes.

Methods

We prospectively examined 50 consecutive patients undergoing EBUS-TBNA for staging of suspected or confirmed NSCLC. We also performed a retrospective chart review of 187 patients undergoing lobectomy or mediastinoscopy for NSCLC.

Results

EBUS-TBNA revealed non-necrotising granulomas in one patient, and in 45 patients it revealed metastatic primary lung malignancy. Surgical lymph node sampling was performed in 187 patients undergoing treatment for, or staging of, NSCLC. Sarcoidal reactions were seen in regional lymph nodes of eight (4.3%) of patients, with all lymph nodes free of metastatic NSCLC (pathologic Stage I) (p = 0.02). Four of these patients were pre-operatively assessed as Stage III (cN2/3). None had a prior history of sarcoidosis or other granulomatous diseases. All eight patients remain alive and recurrence-free.

Conclusions

Sarcoidal reactions are seen in 4.3% of all patients with NSCLC. Metastatic involvement by NSCLC is not seen in lymph nodes exhibiting sarcoidal granulomatous reactions. Non-necrotising granulomas revealed by EBUS-TBNA of lymph nodes during staging of NSCLC should serve to indicate the absence of lymph node metastases.

Introduction

Accurate pre-treatment staging is crucial to direct appropriate management of patients with non-small cell lung carcinoma (NSCLC). The absence of metastatic involvement of mediastinal lymph nodes indicates a better prognosis and such patients are optimally managed with curative resection. Conversely, current management guidelines indicate that optimal management of patients with mediastinal involvement does not include surgery and such patients may be managed with induction therapy or with combination chemoradiotherapy [1]. Minimally invasive mediastinal lymph node staging may be performed using EBUS-TBNA [2]. It has a very high sensitivity and specificity, and recent reports indicate it is equivalent to mediastinoscopy in evaluation anterior paratracheal lymph nodes, and superior in evaluation of the sub-carinal and posterior tracheal regions [3].

Our multidisciplinary lung cancer service routinely uses EBUS-TBNA for minimally invasive staging of NSCLC. We recently experienced one patient in whom fluorodeoxyglucose positron emission tomography (FDG-PET) suggested the presence of hilar and mediastinal lymph node metastases but in whom specimens obtained at EBUS-TBNA demonstrated non-necrotising granulomas. Mediastinal resection at the time of curative lobectomy confirmed the presence of sarcoidal granulomas and, importantly, the absence of lymph node metastases.

In addition to staging the mediastinum in the setting of proven intrapulmonary NSCLC, EBUS-TBNA is able to demonstrate the presence of benign granulomatous disease, such as sarcoidosis [4], [5], [6]. Both sarcoidosis as well as localized sarcoidal reactions are recognised to occur in the setting of malignancy [7], and thus the negative predictive value of pre-operatively identified granulomatous reactions, obtained by minimally invasive EBUS-TBNA, is unclear. This will depend on the pre-test probability of such reactions in NSCLC and, most importantly, the frequency of co-involvement of the two diseases. In this paper we describe the frequency of sarcoidal reactions in patients undergoing evaluation of, or surgical resection for, NSCLC. We also report on the frequency of co-involvement of sarcoidal reactions with metastatic NSCLC in regional lymph nodes in order to allow clearer conclusions to be drawn about patients in whom sarcoidal granulomas are detected on specimens obtained via EBUS-TBNA during pre-operative staging for NSCLC.

Section snippets

Methods

Institutional review board approval was granted for the performance of this study. We examined a prospectively collected cohort of consecutive patients undergoing EBUS-TBNA for staging of suspected or confirmed NSCLC. Only those clinically staged as N2 or N3, by CT chest or FDG-PET, underwent EBUS-TBNA. EBUS-TBNA was performed using a dedicated linear array videobronchoscope (BF-UC180F-OL8, Olympus, Tokyo, Japan) under conscious sedation. Lymph nodes of interest were visualised using EBUS prior

Results

Fifty patients underwent EBUS-TBNA for staging of suspected or confirmed lung cancer. Only one patient had non-necrotising granulomas identified. Two patients had inadequate specimens, two patients had normal lymphoid tissue identified, with the remaining 45 demonstrating NSCLC (39 patients) or small cell lung cancer (6 patients). Findings were confirmed surgically by lymph node dissection in the two patients in whom EBUS-TBNA revealed normal lymphoid tissue, and in the patient in whom

Discussion

This study demonstrates that granulomatous inflammation may be seen in patients with lung malignancy and appears to occur only in early stage disease. The overall incidence of sarcoidal reactions occurring in regional lymph nodes of NSCLC patients was 4.3%. However, such findings were confined to patients with Stage I disease, with an incidence in this group of 7.7%. None of 76 patients with Stages II–IV disease demonstrated sarcoidal reactions in regional lymph nodes (p = 0.02). Most

Conclusions

Sarcoidal reactions in regional lymph nodes may be seen in lung cancer, and appear to be limited to early stage malignancies. A significant proportion of these are radiologically and metabolically occult. On the basis of our results, it appears that metastatic involvement by NSCLC is not seen in lymph nodes exhibiting sarcoidal granulomatous reactions. Therefore, a finding of non-necrotising granulomas on EBUS-TBNA of intrathoracic lymph nodes in the setting of known lung cancer is reliable and

Conflict of interest

No authors have any conflict of interest to declare.

Funding: DPS has received unrestricted stipend support from the National Health & Medical Research Council of Australia.

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Sarcoidal reactions in regional lymph nodes of patients with non-small cell lung cancer: Incidence and implications for minimally invasive staging with endobronchial ultrasound

Abstract

Background

Aims

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conclusions

Conflict of interest

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J Thorac Oncol

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Clin Chest Med

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Clin Dermatol

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Respir Med

Cancer Treat Rev

J Thorac Cardiovasc Surg

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Immunol Lett