The Paradox of Metachronous Lipoid Pneumonia

ABSTRACT

A 70‐year‐old female patient diagnosed with stage IV EGFR‐mutant non–small‐cell lung cancer experienced three distinct instances of exogenous lipoid pneumonia while undergoing chemotherapy. Chest CT consistently revealed ground‐glass opacities with a crazy‐paving pattern, and bronchoscopy confirmed the presence of lipid‐laden, CD163‐positive foamy macrophages. It is noteworthy that each episode was associated with a distinct exogenous exposure: intranasal administration of petroleum jelly, prolonged utilisation of a kerosene heater, and subsequently, intranasal application of Junma Moisturising Oil. The localisation of all episodes to the right middle lobe was noted, and resolution was attained with the cessation of the offending agent. This is the first reported case of recurrent exogenous lipoid pneumonia in a single patient caused by multiple unrelated substances. This case underscores the diagnostic value of radiologic patterns, the significance of meticulous exposure history, and the necessity of contemplating alternative aetiologies in patients with new infiltrates during cancer therapy.

This is a case of recurrent exogenous lipoid pneumonia in a single patient caused by multiple unrelated substances. This case underscores the diagnostic value of radiologic patterns, the significance of meticulous exposure history, and the necessity of contemplating alternative aetiologies in patients with new infiltrates during cancer therapy.

1. Introduction

Exogenous lipoid pneumonia is an uncommon condition caused by the aspiration or inhalation of oily substances, such as mineral oils, animal fats, or petroleum‐based products. While various causative agents have been reported, including petroleum jelly [1, 2], there is a paucity of studies that have compared chest computed tomography (CT) findings based on the type of inhaled substance, particularly within the same individual. Furthermore, the majority of published cases describe a single episode associated with a specific agent. To the best of our knowledge, there have been no reports of recurrent exogenous lipoid pneumonia in a single patient caused by different substances on separate occasions. In this case, the patient exhibited multiple episodes, each initiated by a distinct agent and followed by clinical and radiologic improvement after the elimination of the causative substance. This case offers a distinctive opportunity to observe the temporal and radiographic evolution of exogenous lipoid pneumonia due to varying aetiologies within the same individual.

2. Case Report

A 70‐year‐old woman with stage IV epidermal growth factor receptor (EGFR)‐mutant non–small‐cell lung cancer with brain metastases was receiving osimertinib. As an adverse effect, she experienced recurrent epistaxis with nasal dryness and applied petroleum jelly intranasally. After six months of treatment, a routine chest CT scan performed for tumour evaluation incidentally revealed ground‐glass opacities with interlobular septal thickening and a crazy‐paving pattern in the right middle lobe (Figure 1). To investigate these pulmonary infiltrates, bronchoscopy was performed with differential diagnoses including osimertinib‐induced pneumonitis and carcinomatous lymphangitis. Bronchoalveolar lavage fluid was slightly oily yellow, and cryobiopsy showed clusters of lipid‐laden macrophages in the alveolar spaces that were positive for both CD163 and surfactant protein A, without malignant cells (Figure 2). She was instructed to discontinue the routine intranasal application of petroleum jelly. Three months later, a follow‐up CT scan showed improvement of the opacities without the need for systemic corticosteroid therapy, leading to a diagnosis of exogenous lipoid pneumonia.

FIGURE 1.

Axial high‐resolution chest computed tomography (CT) image obtained 6 months after initiation of osimertinib treatment shows ground‐glass opacities with interlobular septal thickening and a crazy‐paving pattern in the right middle lobe.

FIGURE 2.

Lung tissue obtained by cryobiopsy shows clusters of lipid‐laden CD163‐positive macrophages in the alveolar spaces, with positive staining for surfactant protein A (SP‐A).

Six months later, during the subsequent winter, a follow‐up CT scan (Figure 3A) revealed recurrent opacities in the same region. Further inquiry revealed that the patient had been using a kerosene heater for extended periods of time to maintain an adequate body temperature. It was recommended that she employ alternative, non‐oil‐based methods for heating. After a period of six months, the CT findings demonstrated signs of improvement. During the subsequent winter, a routine follow‐up CT scan revealed significant worsening of the opacities in the aforementioned region (Figure 3B). Despite the patient's claim of refraining from the use of petroleum jelly or kerosene heaters, a detailed history revealed the frequent application of Junma Moisturising Oil, including intranasal use, for the management of severe cutaneous dryness.

FIGURE 3.

(A) Axial CT findings before and after the use of a kerosene heater show worsening of the ground‐glass opacity in the right middle lobe. (B) Axial CT findings before and after the use of Junma Moisturising Oil show worsening of the opacity in the right middle lobe.

In this case, the occurrence and improvement of lipoid pneumonia were observed to occur independently of the progression or regression of the underlying cancer. Furthermore, the onset of lipoid pneumonia did not coincide with the initiation of any anticancer agents. The patient's course of cancer treatment entailed the administration of first‐line osimertinib, followed by carboplatin plus pemetrexed, pembrolizumab, S‐1, vinorelbine, and a subsequent re‐challenge with osimertinib. All episodes of lipoid pneumonia occurred prior to the initiation of pembrolizumab treatment [3]. The patient's demise occurred four years subsequent to the commencement of treatment.

3. Discussion

Exogenous lipoid pneumonia has been observed to manifest with a range of clinical and radiological characteristics. The differential diagnoses of the aforementioned institution encompass a broad spectrum of respiratory pathologies, including but not limited to the following: pulmonary alveolar proteinosis, infectious pneumonia, interstitial lung diseases, lymphoma, and lung cancer. In our case, each of the identified inciting agents—namely, petroleum jelly [1, 2], kerosene heater exposure [4], and moisturising oil [5]—has been previously reported as a cause of exogenous lipoid pneumonia. Although the elimination of the causative agent occasionally results in spontaneous improvement, a standardised treatment for this condition has yet to be established. In cases where the disease progresses or fails to improve, therapeutic options such as lung lavage or corticosteroid therapy may be considered [5].

In the present case, all three episodes of lipoid pneumonia, each caused by a different exogenous agent, were consistently localised to the right middle lobe. The repeated localisation of lesions to the same lobe raises significant considerations regarding anatomical predisposition. Gondouin et al. reported the results of a retrospective multicenter study of 44 cases, which revealed that exogenous lipoid pneumonia most frequently involved the right lung (89%), particularly the middle (89%) and lower lobes (82%) [6]. This phenomenon is likely attributable to gravitational and anatomical factors, including the anatomical characteristics of the right middle lobe bronchus, such as its long, narrow, and dependent course. These characteristics impede the clearance of aspirated lipid material, thereby facilitating its accumulation. In a similar vein, Chieng et al. documented a case of exogenous lipoid pneumonia that exhibited a strong resemblance to lung cancer and was also confined to the right middle lobe [4]. It was emphasised that lipid accumulation frequently follows a peribronchovascular distribution and tends to settle in dependent lung regions, which are anatomically susceptible during aspiration or inhalation events.

It is noteworthy that the patient received chemotherapy, which carries a high risk of drug‐induced lung injury, including agents such as osimertinib and pembrolizumab. However, the pulmonary opacities were ultimately attributed to exogenous lipoid pneumonia caused by various non‐drug–related agents. This case highlights the importance of considering differential diagnoses beyond drug‐induced lung injury and underscores the critical role of thorough history‐taking in identifying exposures that may suggest lipoid pneumonia.

Author Contributions

Kobayashi wrote the main manuscript text and prepared figures. Also, Kobayashi reviewed the manuscript.

Ethics Statement

The manuscript was approved by the institutional review board of the Shizuoka Cancer Center (IRB no. J2025‐15‐2025‐1‐3).

Consent

Written informed consent was obtained for the publication of this manuscript and accompanying images. The form used to obtain consent from the patient complies with the Journal's requirements as outlined in the author guidelines.

Conflicts of Interest

The author declares no conflicts of interest.

Kobayashi H., “The Paradox of Metachronous Lipoid Pneumonia,” Respirology Case Reports 13, no. 9 (2025): e70325, 10.1002/rcr2.70325.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.