Silicosis Mimicking Lung Malignancy: A Case Series

ABSTRACT

Silicosis, an important occupational disease, is caused by inhalation of silicon dioxide and can lead to pulmonary inflammation and fibrosis. Silicosis can be misdiagnosed for malignant disease, as both can present with hypermetabolic lesions on FDG‐PET imaging. This case series describes three patients who were suspected to have a primary lung malignancy based on FDG‐PET findings, but were found to have pulmonary silicosis. With this series, we demonstrate how histologic examination can differentiate between silicosis and malignancy and provide suggestions to help clinicians differentiate between these two illnesses.

This case series describes three patients that were suspected to have a primary lung malignancy based on FDG‐PET findings, but were found to have pulmonary silicosis. With this series, we demonstrate how histologic examination can differentiate between silicosis and malignancy and provide suggestions to help clinicians differentiate between these two illnesses.

1. Introduction

Silicosis, an important occupational disease, is caused by inhalation of silica (SiO₂ or silicon dioxide). Silica exists either as uncombined or free silica, such as crystalline silica or amorphous silica, or as a combined form such as silicates. Crystalline silica is considered to be toxic, with biological activity occurring if particles are small enough to reach the terminal bronchioles and alveoli. These particles are generally less than 5 μm in diameter and are called ‘respirable crystalline silica’ (RCS) [1]. Inhalation of RCS causes inflammation and can eventually progress to pulmonary fibrosis [2].

Three forms of silicosis have been described, based on initial exposure to RCS and onset of symptoms [3].

Acute silicosis: also called silicoproteinosis, a form that is rare and only seen in patients with high‐intensity RCS exposure (e.g., sandblasting). The onset typically is within weeks to less than 5 years after exposure. Histopathology shows alveolitis and alveolar proteinosis, hence the name silicoproteinosis.

Accelerated silicosis: in accelerated silicosis, symptoms develop within 5–10 years after exposure, and this form overlaps with both acute and chronic silicosis. Pathologic examination can show both alveolar proteinosis as well as silicotic nodules typical of chronic disease.

Chronic silicosis: chronic silicosis can be divided into simple and complicated silicosis. Usually, symptoms develop 10–30 years after exposure to low concentrations of RCS. Simple silicosis is also called nodular silicosis, due to the appearance of typical pulmonary nodules less than 10 mm in diameter. As nodules progress, simple silicosis can progress to complicated silicosis (also called pulmonary massive fibrosis, PMF), which is characterised by the expansion of the nodules leading to pulmonary destruction.

In this case series, we present three patients who were suspected to have lung malignancy based on FDG‐PET ((F‐18)‐2‐fluoro‐2‐deoxy‐D‐glucose—Position Emission Tomography) findings, in which histopathologic examinations showed silicosis.

2. Case Series

2.1. Case 1

A 67‐year‐old male was referred to our outpatient clinic with a cavitating mass in the left upper lobe (Figure 1a). FDG‐PET showed a hypermetabolic, partially cavitating tumour (Figure 1b, standard uptake value (SUV) max 7.41), with slight to moderate activity in bilateral hilar lymph nodes. The patient is a former smoker with at least 75 pack years. He used to be a metalworker. A bronchoscopy was performed to investigate infectious causes. Cultures showed no bacterial or fungal growth. Follow‐up CT after 3 months showed no change. An XperGuide of the lesion was performed. Due to haemoptysis, only one biopsy was taken. Histologic examination showed sclerotic lung tissue with no signs of malignancy, but there was doubt whether it was a representative sample of the lesion. A Video Assisted Thoracic Surgery (VATS) lobectomy, converted to a thoracotomy due to extensive adhesions to the thoracic wall, was performed. Macroscopic examination of the resection specimen revealed a subpleural tumour with central cavitation and a diameter of 2.5 cm (Figure 2a). Histologic examination showed fibrosis, depositions of antracotic pigment and silicotic nodules (Figure 2b). The post‐operative course was complicated due to prolonged leakage of air, which required two more surgical procedures, and hospital‐acquired pneumonia. The patient was treated with antibiotics.

FIGURE 1.

(a) Axial CT image shows a cavitating lesion in the left upper lobe with a thickened wall. (b) FDG‐PET CT shows increased activity in the thickened wall.

FIGURE 2.

(a) Subpleural mass with central cavitation in pathology specimen. (b) Low‐power view of the subpleural mass showing fibrotic lung tissue with peripheral sclerotic regions containing dust‐laden macrophages (➔). Red * indicates parietal pleura.

2.2. Case 2

An 81‐year‐old male was referred by an ENT specialist to our outpatient clinic with a mass in the right upper lobe as seen on CT neck. CT neck was performed as he complained of pain on the right side of the neck and in the right ear, and demonstrated a speculated tumour of 31 mm with suspected local invasion of the pleura (Figure 3a,b). The patient is a non‐smoker and former construction worker, having worked with both metal and concrete. On FDG‐PET, both the tumour in the right upper lobe (Figure 3c, SUV max 7.44) as well as right hilar and mediastinal lymph nodes were hypermetabolic (SUV max 6.81). T1‐weighted image showed an enhanced superior sulcus mass without involvement of the brachial plexus (Figure 3d). EUS (Endoscopic Ultrasound) of the hypermetabolic subcarinal lymph node (Naruke 7) was performed. Histologic examination showed lymph node tissue with sclerotic changes, without malignant cells. Based on a high suspicion of lung malignancy with the appearance of lymphogenic metastasis, a mediastinoscopy was performed of Naruke 2 (left and right), Naruke 4 (left and right) and Naruke 7. Histologic examination demonstrated reactive changes with histiocytic infiltrate and fibrosis, but no malignancy. As follow‐up CT after 2 months showed subtle growth of the right upper lobe mass, a lobectomy of the right upper lobe and lymph node dissection were performed. Intra‐operatively, there were notable adhesions connecting the right lung to the thoracic wall, diaphragm, and mediastinum. Lymph nodes were also fixed in their surrounding tissue. Pathologic evaluation revealed a subpleural mass with a diameter of 3 cm. Microscopic examination showed fibrotic tissue with histiocytic infiltrate and lymphoid hyperplasia. The fibrotic changes extended into the parietal pleura. In both the lesion and the mediastinal lymph nodes, there were extensive depositions of silica crystals with the forming of silicotic nodules and antracotic pigment (Figure 4). The patient is included in follow‐up with lung function tests.

FIGURE 3.

(a) Axial CT image in lung setting shows a spiculated lesion in the right upper lobe. (b) Axial CT image with intravenous contrast in soft tissue setting shows enhancement of the lesion. (c) FDG‐PET CT shows increased activity of the right upper lobe mass. (d) Sagittal T1‐weighted image with intravenous Gadolinium shows an enhancing superior sulcus mass; there is no involvement of the brachial plexus.

FIGURE 4.

Low‐power view of fibrotic lung lesion containing residual air spaces, silicotic nodules (➔) and chronic inflammation with scattered lymphoid follicles (black *). Red * indicates parietal pleura.

2.3. Case 3

A 71‐year‐old male with idiopathic pulmonary fibrosis (IPF), receiving treatment in our outpatient clinic, was found to have hilar and mediastinal lymphadenopathy on follow‐up CT (Figure 5a). The patient is a former smoker (64 pack years) and had worked in construction, including work with heavy metals. FDG‐PET demonstrated hypermetabolic lymph nodes mediastinal right (SUV max 16.57), supraclavicular right, hilar right, and axillary/infraclavicular left (Figure 5b). There were no intrapulmonary hypermetabolic lesions. Mediastinoscopy was performed of Naruke 2 right. Histologic examination indicated no malignancy, but sclerotic tissue with the presence of antracotic pigment and birefringent crystals (Figure 6). Energy Dispersive X‐ray (EDX) analysis indicated the presence of silica, aluminium, and potassium, as well as pure silica crystals. Two yearly high resolution (HR) CT follow‐up was planned regarding IPF monitoring.

FIGURE 5.

(a) Axial CT image shows an enlarged lymph node on level 2R. (b) FDG‐PET CT shows increased activity of the lymph node.

FIGURE 6.

High‐power view of silicotic nodule with peripheral histiocytic infiltrate containing anthracotic pigment and crystals.

3. Discussion

Lung cancer is the leading cause of cancer‐related deaths worldwide. These cases show that based on radiology findings alone, it can be challenging to differentiate between silicosis and lung malignancy. In thoracic oncology, FDG‐PET is commonly used in the diagnostic trajectory and is recommended in patients that are eligible for treatment with curative intent [4]. FDG uptake, however, as this series also illustrates, is not specific to malignancy and occurs also in inflammation or infection [5, 6]. In patients with both chronic silicosis as well as acute silicosis, hypermetabolic nodules/lesions on FDG‐PET have been described mimicking malignancy [7, 8, 9, 10]. It is thought that the inflammatory response of the body to RCS, mainly the activity of neutrophils, leads to FDG uptake [1]. In silicosis—as this case series also illustrates—SUV max values can be in the malignant range. This means that in the case of high SUV max values, SUV max values do not help differentiate between silicosis and malignancy [7]. The use of biomarkers including pro‐ and anti‐inflammatory cytokines in silicosis is under investigation, but more research is needed to improve sensitivity and specificity [11]. Volatile organic compounds (VOCs) in exhaled breath are promising as non‐invasive biomarkers for exposure to silica [12], as well as screening for lung cancer [13].

Today, however, only histopathological examination can differentiate between malignancy and silicosis in hypermetabolic lesions, and even then, it might be necessary to sample multiple lesions to exclude the presence of malignant cells.

Less invasive techniques can be considered to sample suspect lesions, such as navigational bronchoscopy. Frozen sections could also be considered to minimise the need for lobectomy, as well as performing a segmentectomy with suspected lesions less than 2 cm to minimise loss of lung function. It should be noted that even though histopathology shows no malignant cells, patients with silicosis do have an increased risk of developing lung malignancy (both carcinoma and mesothelioma) and should be (closely) monitored [14, 15, 16].

Author Contributions

Titia van Duin and Franz Schramel came up with the conception of the work. Titia van Duin drafted the first version of the work. Franz Schramel, Carmen Ambarus, Sophie van der Mark and Wouter van Es contributed to the text, critically revising it. Carmen Ambarus selected the pathology images and provided explanations in the text (and figure legends). Wouter van Es selected the radiology images, providing necessary explanations in the text and figure legends. All authors approved the final version of the manuscript to be published.

Consent

Individual patient consent was acquired for publication from each patient involved in the case series. All patients signed the journal's consent form.

Conflicts of Interest

The authors declare no conflicts of interest.

van Duin T., Ambarus C., van Es W., van der Mark S., and Schramel F., “Silicosis Mimicking Lung Malignancy: A Case Series,” Respirology Case Reports 13, no. 7 (2025): e70298, 10.1002/rcr2.70298.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.