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Table of Contents
ORIGINAL ARTICLE
Year : 2018  |  Volume : 20  |  Issue : 1  |  Page : 12-16

Does anthracosis reported in endobronchial ultrasound-guided transbronchial needle aspiration exclude metastasis?


1 Department of Pulmonary Diseases, Ankara University, Ankara, Turkey
2 Department of Pulmonary Diseases, Dr. Suat Seren Chest Diseases and Thoracic Surgery Teaching and Research Hospital, Izmir, Turkey
3 Department of Pathology, Dr. Suat Seren Chest Diseases and Thoracic Surgery Teaching and Research Hospital, Izmir, Turkey

Date of Web Publication4-May-2018

Correspondence Address:
Dr. Serhat Erol
Ankara University, Cebeci Hospital Pulmonary Diseases Department, Mamak, Ankara, 06112
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejop.ejop_5_18

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  Abstract 


OBJECTIVES: In some studies, it has been hypothesized that anthracotic pigmentation in mediastinal lymph nodes is a sign of benign conditions and excludes metastasis from thoracic and extrathoracic malignancies. The aim of this study was to evaluate the clinical significance of mediastinal lymph node anthracosis in cancer patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).
MATERIALS AND METHODS: In this study, medical data of patients with lung cancer or extrathoracic cancer who underwent EBUS-TBNA for investigation of mediastinal lymph node metastasis were evaluated retrospectively. EBUS-TBNA cytology reported as anthracotic pigmentation was included in this study. Patients were excluded from the study if cytology of aspirated lymph nodes reported as “benign,” “malignancy,” or “granulomatous inflammation.”
RESULTS: There were 50 eligible patients. Thirty-one (62%) patients underwent EBUS-TBNA for lung cancer staging and 19 (38%) for evaluation of extrathoracic metastasis. A total of 120 lymph nodes were sampled. The most sampled station was subcarinal. EBUS-TBNA was false negative in eight of 31 (25.8%) lung cancer patients and one of 19 (5.2%) extrathoracic malignancy patients.
CONCLUSIONS: Anthracotic pigmentation of lymph nodes in EBUS-TBNA cannot exclude metastasis in lung cancer patients and mediastinoscopy should be performed before surgery in this group. In patients with extrathoracic malignancy, anthracotic pigmentation is associated with benign conditions. However, further investigation with larger cohort is needed.

Keywords: Anthracosis, endobronchial ultrasound-guided, interventional pulmonology, thoracic cancer


How to cite this article:
Erol S, Anar C, Erer OF, Aydogdu Z, Aktogu S. Does anthracosis reported in endobronchial ultrasound-guided transbronchial needle aspiration exclude metastasis?. Eurasian J Pulmonol 2018;20:12-6

How to cite this URL:
Erol S, Anar C, Erer OF, Aydogdu Z, Aktogu S. Does anthracosis reported in endobronchial ultrasound-guided transbronchial needle aspiration exclude metastasis?. Eurasian J Pulmonol [serial online] 2018 [cited 2018 Nov 16];20:12-6. Available from: http://www.eurasianjpulmonol.com/text.asp?2018/20/1/12/231811




  Introduction Top


Mediastinal lymph node metastasis is one of the most important determinants of treatment decision and prognosis in patients with pulmonary or extrathoracic malignancies (ETM). There may be other benign reasons such as tuberculosis (TB) or sarcoidosis for Mediastinal lymphadenopathy (MLA) in cancer patients.[1],[2] Anthracosis which is one of these benign conditions can also cause false-positive positron emission computed tomography (PET/CT) mimicking malignancy.[3],[4],[5],[6]

In cancer patients with MLA, it is mandatory to obtain lymph node samples before treatment decision. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become standard diagnostic procedures in cases with MLA. It has been hypothesized that in nonsmall cell lung cancer patients, anthracotic particles in lymph nodes can prevent lymph nodes from metastasis.[7]

The aim of this study was to evaluate the clinical significance of mediastinal lymph node anthracosis in cancer patients who underwent EBUS-TBNA.


  Materials and Methods Top


Study population

We retrospectively analyzed the medical data of patients with known lung cancer or ETM who underwent EBUS-TBNA for lung cancer staging or diagnosis of mediastinal metastasis of ETM. Patients with positive confirmation by mediastinoscopy or with at least 1-year follow-up after EBUS-TBNA were enrolled in this study.

All procedures were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki Declaration. Informed consent was obtained from all patients.

The work was approved by the Institutional Review Board.

Inclusion and exclusion criteria

Patients were included in the study if cytology of aspirated lymph nodes reported as anthracosis and excluded from the study if reported as “benign,” “malignancy,” or “granulomatous inflammation.”

Definitions of false negative and true negative

EBUS-TBNA was accepted as “false negative” if mediastinoscopic pathology of lymph nodes was reported as malignancy or lymph node diameter on CT or metabolic activity on PET/CT increased during follow-up.

If mediastinoscopy confirmed anthracosis or during follow-up, CT or PET/CT did not reveal lymph nodes enlargement or increased metabolic activity EBUS-TBNA accepted as “true negative.”

Endobronchial ultrasound-guided transbronchial needle aspiration procedure

All EBUS-TBNA procedures were performed by the same bronchoscopist. The EBUS-TBNA procedure was performed by an convex probe EBUS-guided TBNA bronchoscope (7.5 MHz, BF-UC160F; Olympus Optical Co, Tokyo, Japan) under conscious sedation. Vital signs patients were monitored during the procedure. Each target nodal station was punctured at least twice, and one or more tissue core specimens were obtained. The cytology specimens were smeared onto slides and air dried and stained and also cell blocks were prepared for every patient.

For the cell blocks, aspirated material was ejected into saline solution, embedded in paraffin, and thin sections were obtained.

The rapid on-site evaluation was not available at our institution.

Final diagnosis

LN accepted as 'malignancy' if microscopic examination revealed malignant cells, and as 'granulomatous inflammation' if granulomas have been demonstrated. If the microscopic examination of LN aspiration specimens revealed anthracotic pigments, the LN was accepted as anthracotic lymphadenitis. LN accepted as 'reactive adenitis' if microscopic examination showed none of the malignant cells, granulomatous inflammation or anthracotic pigmentation.


  Results Top


A total of 191 patients – 125 for lung cancer stating and 66 for the diagnosis of ETM metastasis - underwent EBUS-TBNA. Of these, 50 patients were included according to the criteria explained above. There were 35 male and 15 female patients aged between 36 and 83. Forty-eight patients had PET/CT and standard uptake value (SUV) of lymph nodes were between 2 and 18. The characteristics of patients are shown in [Table 1].
Table 1: Clinical features of patients and number of sampled lymph nodes

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Thirty-one (62%) patients underwent EBUS-TBNA for lung cancer staging and 19 (38%) for the evaluation for mediastinal metastasis of ETM. A total of 120 lymph nodes with diameters between 8 mm and 34 mm were sampled. The most sampled stations were subcarinal [7] and the right lower paratracheal (4R) lymph nodes. In nearly half of the patients, two lymph node stations were sampled [Table 1].

Of 31 lung cancer patients, 23 underwent mediastinoscopy for confirmation and eight had radiological follow-up. Lymph node metastasis was shown with mediastinoscopy in 6 (19.3%) patients. In two (6.5%) patients, lymph node diameters were increased during radiological follow-up [Table 2]. As a result, EBUS-TBNA was false negative in 8 of 31 (25.8%) lung cancer patients.
Table 2: Results of endobronchial ultrasound-guided transbronchial needle aspiration and follow-up according to groups

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Eight of 19 ETM patients underwent mediastinoscopy for confirmation and all of them were negative for lymph node metastasis. The remaining 11 patients were radiologically followed up, and in one patient, progression of mediastinal lymph node enlargement was reported [Table 2]. EBUS-TBNA was false negative in 1 of 19 (5.2%) ETM [Figure 1].
Figure 1: Diagnostic workup and follow-up results. EBUS-TBNA: Endobronchial ultrasound-guided transbronchial needle aspiration, ETM: Extrathoracic malignancy

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As a result, EBUS-TBNA reported as anthracosis was false negative in 25.8% of lung cancer and 5.2% of EMT patients.


  Discussion Top


In this retrospective study, we evaluated the clinical implication of anthracotic pigmentation reported in EBUS-TBNA. Anthracosis is black pigmentation which is not only caused by coal dust but also other occupational and environmental exposures such as air pollution, biomass fuels used for cooking, smoking, and previous TB.[8],[9] Lymph node anthracosis can cause mediastinal lymph node enlargement on CT and can be false-positive mimicking lung cancer.[3],[4],[5],[6],[7] Possible explanation for false-positive PET/CT is increased cellular activity and ongoing inflammation.[9],[10]

Kirchner et al.[4] and Yilmaz Demirci et al.[6] reported lymph node anthracosis diagnosed with EBUS. Both studies included patients with known pulmonary and extrapulmonary malignancies. All of these anthracotic lymph nodes were confirmed as benign with mediastinoscopy or radiological follow-up.

Park et al.[7] reported that only 4.9% of lymph nodes were malignant with mediastinoscopy in operable nonsmall cell lung cancer patients with microscopic anthracotic pigment in EBUS-TBNA specimens. They concluded that the accumulation of anthracotic particles could impair trapping malignant cells in lymph nodes.

In our study, anthracosis was not associated with benign conditions in lung cancer staging group. False-negative results in this group were higher contrary to the previous studies.[4],[6],[7] This might be due to number of sampled lymph node stations, number of passes for each lymph nodes or as Park et al.[7] mentioned, sampling of only PET/CT positive lymph nodes may be the reason for high false-negative results.

The European Society of Thoracic Surgeons (ESTS) guidelines recommend preoperative surgical staging in case of a negative endosonography because probability of having mediastinal nodal involvement for any individual patient with a negative endosonography result is 13%–15%.[11] Furthermore, meta-analysis revealed that mediastinoscopy has fewer false negatives.[12] For lung cancer staging, anthracosis does not exclude metastasis and mediastinoscopy should be performed as ESTS recommended in cases with negative EBUS-TBNA.

In our study, we found false-negative rate as 5.2% in ETM group which was less than lung cancer group. The previous studies revealed the high specificity and sensitivity of EBUS-TBNA in detection of mediastinal lymph node metastasis of ETM.[2] In this group of patients, nearly half of the patients had benign conditions that cause mediastinal lymph node enlargement. Moreover, anthracosis is one of the frequently seen benign conditions. Although false-negative results can be seen with anthracosis, it is rare.[13],[14],[15],[16] Thus, we think that it may be more appropriate to have occupational and environmental exposure history, CT images, and smoking history of the patient before further invasive diagnostic procedures in patients with ETM. Radiological follow-up may be more appropriate instead of surgical procedures in this group of patients.

CT findings can be used to differentiate enlarged anthracotic lymph nodes from malignant lymph node enlargement. Kirchner et al. found that the most common site of anthracotic lymph nodes was the subcarinal area.[17] In the same study, they reported that malignant lymph nodes had a higher frequency of ill-defined contours, nodal necrosis, and anthracotic lymph nodes showed calcification more often. Granulomatous inflammation shown to be a sign of benign conditions in patients with ETM.[18] Moreover, anthracosis may also be accepted as a sign of benign conditions in this group of patients.

In low- and middle-income countries, industrialization and related air pollution and exposure to indoor biomass fuel smoke, especially homemakers while cooking, cause higher incidence of anthracosis.[19] Furthermore, association between anthracosis and TB was shown in many studies.[20],[21],[22],[23],[24],[25] Anthracosis also can cause pulmonary mass and mediastinal lymphadenopathy and false-positive PET results and may be erroneously diagnosed as lung cancer and/or lymph node metastasis.[3],[4],[5],[6],[7],[8],[9],[10],[23],[26] Therefore, in patients with or without known malignancy, mediastinal lymphadenopathy with high SUV may be due to anthracosis, metastasis, MTLA, or coincidence of these conditions. Thus, clinicians have to make a proper differential diagnosis and rule out possible conditions with patient history, cytology, and microbiological examination.

Our study has some limitations. First, it is a retrospective study with a limited number of patients. Second, EBUS-TBNA was not confirmed with mediastinoscopy in all patients.


  Conclusions Top


Anthracosis of lymph nodes in EBUS-TBNA cannot exclude metastasis in lung cancer patients and mediastinoscopy should be performed before surgery. In patients with extrathoracic malignancy, anthracotic pigmentation in EBUS-TBNA specimens is associated with benign conditions. However, larger confirmation studies are needed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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