Lipoid pneumonia mimicking lung cancer: a retrospective case series and literature review

Abstract

Background

Lipoid pneumonia (LP) is a rare inflammatory lung disease caused by lipid accumulation in alveolar spaces. Its nonspecific clinical and radiological features often lead to misdiagnosis as lung cancer, resulting in potentially avoidable surgical interventions.

Methods

We conducted a retrospective case series of six patients who underwent surgical resection at our institution between 2019 and 2025 with a preoperative suspicion of lung cancer but were ultimately diagnosed with LP by postoperative histopathology. Clinical presentations, imaging features, tumor marker levels, and pathological findings were analyzed.

Results

All six patients had pulmonary nodules or masses highly suggestive of malignancy on chest CT, including ground-glass opacities, spiculated margins, and cystic changes. Two patients had elevated tumor markers (CEA (carcinoembryonic antigen) or NSE (neuron-specific enolase)). Final pathological examination revealed intra-alveolar lipid-laden macrophages, cholesterol clefts, and chronic granulomatous inflammation, consistent with LP. Most patients denied a specific history of lipid aspiration, though one case had a habit of applying intranasal cooling oil.

Conclusions

LP can closely mimic lung cancer both radiologically and biochemically. A high index of suspicion is required in patients with atypical pulmonary lesions, even when tumor markers are elevated. Pathological examination remains the gold standard for diagnosis. Early recognition may help avoid potentially avoidable surgery.

Introduction

Lipoid pneumonia (LP) is a rare inflammatory condition characterized by lipid accumulation in the alveoli. Due to its nonspecific radiological features, often presenting as spiculated masses or ground-glass opacities, it frequently mimics lung cancer, posing a significant diagnostic challenge. This study analyzes six cases of LP mimicking malignancy to identify key clinicopathological pitfalls and reduce potentially avoidable major resections. This study reviews and analyzes the clinicopathological features of six cases of LP confirmed by surgical pathology in our hospital, combined with a literature review, to deepen the understanding of this disease and provide a reference for precise clinical diagnosis and treatment.

This was a retrospective case series conducted at the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China. We retrieved the clinical data of six consecutive patients who underwent surgical resection between January 2019 and September 2025 with a preoperative suspicion of lung cancer but were postoperatively diagnosed with LP by histopathology.

Clinical data, including demographics, symptoms, imaging findings, laboratory results (including tumor markers), and pathological reports, were collected. All patients underwent video-assisted thoracoscopic surgery (VATS) or robotic-assisted resection. Histopathological examination was performed on formalin-fixed, paraffin-embedded tissue sections using hematoxylin and eosin (H&E) staining. The diagnosis was primarily established based on morphological features observed in H&E staining. Immunohistochemistry (IHC) served only as an ancillary tool to provide supportive evidence. Specifically, Ki-67 was used to assess cell proliferation, and CEA was utilized as its expression is typically lower in reactive lesions compared to most carcinomas. Special stains, including Periodic Acid-Schiff (PAS), Hexamine Silver (GMS), and Acid-Fast staining, as well as TB-DNA PCR amplification, were utilized to screen for fungal or mycobacterial infections.

This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study protocol was approved by the Ethics Committee of the Seventh Affiliated Hospital of Sun Yat-Sen University (Approval No. KY-2025-506-01).

Case 1

A 41-year-old female presented with a persistent right lower lobe ground-glass opacity (GGO) with a cystic component, detected four years prior (Fig. 1A). While the size remained stable, increasing density on follow-up raised suspicion for indolent adenocarcinoma (Fig. 1C and D). Consequently, she underwent VATS(single-port video-assisted thoracoscopic) wedge resection on July 24, 2024. Postoperative pathology revealed extensive lymphocyte infiltration in the subpleural alveolar septa, foamy macrophage-like cells (Fig. 1E), and a small amount of cholesterol crystal deposition within some alveolar spaces. The alveolar epithelium exhibited mild hyperplasia. Pathology indicated LP of the right lower lobe.

Fig. 1.

Imaging and pathological findings of Case 1. A Axial chest CT (lung window, November 2020) reveals a subpleural ground-glass opacity nodule in the right lower lobe. B Follow-up CT (November 2021) indicates that the nodule persisted without any significant change. C Follow-up CT (November 2022) indicates that the ground opacity has increased in the nodule. D Follow-up CT (July 2024) indicates that ground opacity has increased in the nodule compared to November 2022. E Postoperative pathological section (H&E stain, ×200), displaying foamy macrophages (indicated by the arrow in yellow) and cholesterol cleft deposition (indicated by the arrow in black) within the alveolar spaces

Long-term follow-up data for this patient was unavailable.

Case 2

A 27-year-old asymptomatic female presented with a right middle lobe nodule discovered one year prior. Follow-up CT revealed a cavitary nodule (15 × 9 mm) with slight wall thickening (Fig. 2A). A subsequent scan showed a mixed-density lesion with vacuole sign and pleural indentation (Fig. 2B), prompting VATS wedge resection on September 10, 2025.

Fig. 2.

Imaging and pathological findings of Case 2. A Axial chest CT (lung window, from an outside hospital, July 2024) showing a cavitary nodule in the right middle lobe. B Axial chest CT (lung window, September 2025) reveals a mixed-density nodule with pleural indentation and the vacuole sign. C Postoperative pathological section (H&E stain, ×200) displaying numerous cholesterol clefts (indicated by arrow in black) encircled by inflammatory cells and giant cells(indicated by the arrow in yellow)

The postoperative pathological examination of the resected specimen showed lung tissue containing numerous cholesterol crystals, accompanied by a substantial infiltration of lymphocytes, plasma cells, and a multinucleated giant cell reaction. The pathological findings were consistent with chronic non-specific inflammation. No distinct suspicious fungal elements were observed on H&E sections. Molecular testing for Tuberculosis (TB-DNA) was negative. The final pathological diagnosis was chronic granulomatous inflammation of the right middle lobe, consistent with endogenous (cholesterol) lipoid pneumonia.

Case 3

A 56-year-old female presented with “a shadow in the right lower lung found on chest CT for three weeks.” The patient had a chest CT scan for trauma, which showed a sub-solid patchy opacity in the posterior basal segment of the right lower lobe, measuring approximately 25 × 35 mm, highly suspicious for invasive adenocarcinoma (Fig. 3A). Laboratory tests were positive for parainfluenza virus IgM antibody and T-SPOT and negative for tumor markers. To obtain a definitive diagnosis, a CT-guided lung biopsy was performed first. The pathology indicated “scant tissue, alveolar epithelial hyperplasia with hyperchromatic nuclei, and some cells showing a ‘hobnail’ pattern, atypical epithelial hyperplasia with regenerative changes, which could not definitively exclude malignancy in the clinical context (Fig. 3B). The patient underwent a “VATS right lower lobectomy” on December 15, 2022. Postoperative paraffin-embedded pathology revealed alveolar epithelial cell hyperplasia, with a large number of foamy macrophages in some alveolar spaces. Occasional areas showed cholesterol crystal formation and foreign body giant cell reaction. The local interstitium had mild connective tissue proliferation with focal infiltration of lymphocytes, plasma cells, and occasional eosinophils, consistent with inflammatory changes(Fig. 3C). Special stains (Alcian Blue, PAS, Hexamine Silver, and Acid-fast) were consistently negative, excluding specific infectious granulomas (fungal or mycobacterial).Pathology indicated LP of the right lower lobe.

Fig. 3.

Imaging and pathological findings of Case 3. A Axial chest CT (lung window) reveals a sub-solid patchy opacity in the right lower lobe, adjacent to the pleura. B CT-guided lung biopsy pathology section (H&E stain, ×200) indicated scant tissue, alveolar epithelial hyperplasia with hyperchromatic nuclei, and some cells showing a ‘hobnail’ pattern, could not definitively exclude malignancy in the clinical context. C Postoperative pathology section (H&E stain, ×200) displaying a large number of foamy macrophages (indicated by the arrow in yellow) and cholesterol crystal formation (indicated by the arrow in black)

Upon postoperative review of the patient’s history, it was revealed that the individual had a habit of applying cooling oil to the nose.

During the postoperative follow-up, a chest CT at one year revealed multiple new ground-glass nodules scattered in both lungs. However, a subsequent scan at three years post-surgery showed that these nodules had spontaneously disappeared. This spontaneous resolution further supports the diagnosis of a benign inflammatory process rather than malignancy.

Case 4

A 71-year-old male presented with a 20-day history of cough and chest pain. Chest CT revealed a multiloculated cystic nodule (20 × 25 mm) in the left lower lobe (Fig. 4A). Follow-up imaging showed irregular cyst wall thickening (Fig. 4B), classified as a high-risk nodule. He underwent VATS wedge resection on July 18, 2024. Postoperative pathology reported scattered multifocal alveolar epithelial hyperplasia with bronchial epithelial metaplasia in the lung tissue. The alveolar septa showed lymphoid hyperplasia, forming small clusters that protruded into the alveolar spaces in a bud-like fashion, covered by hyperplastic type II pneumocytes. The alveolar spaces contained a variable number of foamy macrophages(Fig. 4C). IHC analysis demonstrated that the hyperplastic alveolar epithelium was positive for CK7 and TTF-1 (indicating reactive type II pneumocytes), while the intra-alveolar foamy cells were strongly positive for CD68, confirming them as macrophages rather than tumor cells.Pathology indicated LP with organizing pneumonia in the left lower lobe.

Fig. 4.

Imaging and pathological findings of Case 4. A Axial chest CT (lung window, January 2024) reveals a multiloculated cystic nodule in the posterior basal segment of the left lower lobe. B Follow-up CT (Jul 2024) reveals irregular thickening of the cyst wall (indicated by the arrow). C Postoperative pathological section (H&E stain, ×400) displaying a large number of foamy macrophages (marked by the arrow in yellow) filling the alveolar spaces, along with widened alveolar septa and lymphocytic infiltration

During the postoperative follow-up period, the patient remained disease-free with no radiological evidence of recurrence.

Case 5

A 34-year-old male was admitted with a history of intermittent hemoptysis for four months and a right upper lobe mass discovered over three months prior. A chest CT scan from an external hospital revealed a lesion in the right upper lobe, approximately 30 by 19 mm in size, with spiculated margins and an ill-defined border (Fig. 5A and B). Differential diagnoses included inflammatory granuloma or a neoplasm. Tumor marker analysis revealed elevated NSE (18.17 ng/mL). Despite a slight reduction in lesion size following a course of antibiotics (cefuroxime/sulbactam), the spiculated mass and mediastinal lymphadenopathy persisted. Due to the high suspicion of malignancy and patient anxiety, a VATS right upper lobectomy was performed on December 27, 2019. Postoperative paraffin-embedded pathology revealed focal destruction of the normal alveolar structure. The remaining alveolar spaces were filled with numerous foamy macrophages (Fig. 5C). The alveolar septa displayed nodular lymphoid hyperplasia, protruding into the alveolar spaces in a bud-like manner. The remaining alveolar epithelium was hyperplastic, arranged in a glandular pattern. The periphery exhibited significant fibrous tissue proliferation. A large number of plasma cells and lymphocytes were observed around the local bronchi. The morphological changes were consistent with an inflammatory lesion. Significantly, special stains were positive for PAS and Hexamine Silver (GMS), revealing fungal hyphae consistent with Aspergillus species. Auxiliary IHC results showed the proliferating epithelium was TTF-1(+) but with extremely low Ki-67 labeling and negative CEA, which supported the benign nature of the lesion. The final diagnosis was Endogenous Lipoid Pneumonia secondary to fungal infection.

Fig. 5.

Imaging and pathological findings of Case 5. A Contrast-enhanced chest CT (lung window) revealing a mass with spiculated margins (indicated by the arrow) and surrounding patchy consolidation in the right upper lobe. B Contrast-enhanced chest CT (mediastinal window): The lesion exhibits heterogeneous enhancement, with internal patchy non-enhancing areas, and a CT value of approximately 55 HU. C Postoperative pathological section (H&E stain, ×200) reveals the destruction of alveolar structures, extensive infiltration with foamy macrophages (indicated by arrow in yellow), nodular lymphoid hyperplasia (indicated by arrow in black), and dense accumulation of plasma cells and lymphocytes. D High-power view (PASM stain, ×400) revealing fungal hyphae consistent with Aspergillus species (indicated by arrow in black)

Case 6

A 64-year-old female patient presented with the discovery of a “right upper lobe mass” three months ago. During a health check-up in May 2024, a chest CT scan detected a large mass in the right upper lobe, measuring approximately 76 × 52 × 49 mm with indistinct borders and irregular margins (Fig. 6A and B). Its internal density was heterogeneous, with multiple patchy high-density areas observed, exhibiting a CT value of around 109 Hounsfield Units (HU). Laboratory tests indicated persistently elevated levels of carcinoembryonic antigen (CEA) at 21.1 ng/mL (reference range: <5.00 ng/mL). A CT-guided biopsy performed at our hospital did not detect any tumor. Bronchoscopy revealed complete obstruction of the posterior segmental bronchus of the right upper lobe, with mucosal infiltration and surface necrosis (Fig. 6C). The patient temporarily refused to be hospitalized for further treatment due to family matters and requested to be observed for three months before re-examination. A subsequent CT scan on July 8, 2024, showed an irregular mass in the right upper lobe, measuring approximately 73 × 49 × 46 mm. The CT value was approximately 90 HU. The CEA value was 21.57 ng/mL (reference range: <5.00 ng/mL). Due to the large size of the mass and persistently high levels of CEA, malignancy was highly suspected. On July 15, 2024, the patient underwent a “robot-assisted right upper lobe bronchial sleeve resection.” Following the operation, CEA levels normalized. Postoperative pathology revealed extensive infiltration of lymphocytes, plasma cells, and eosinophils in the large bronchial wall and alveolar septa, along with the formation of lymphoid follicles (Fig. 6D). The alveolar spaces contained a variable number of foamy macrophages and multinucleated giant cells. A small focus of Aspergillus was observed in an individual alveolus using Hexamine Silver staining(Fig. 6E). IHC analysis showed the foamy cells were CD68(+).Pathology indicated Lipoid Pneumonia of the right upper lobe, likely secondary to proximal bronchial obstruction by the fungal inflammation.

Fig. 6.

Imaging, endoscopic, and pathological findings of Case 6. A Non-contrast chest CT (May 2024) showing an irregular mass in the right upper lobe with irregular margins, heterogeneous internal density, and multiple patchy high-density shadows. B Contrast chest CT (July 2024) revealing an irregular mass in the right upper lobe with heterogeneous enhancement. C Bronchoscopy revealed a complete obstruction of the posterior segmental bronchus of the right upper lobe due to a necrotic and infiltrative lesion. D Postoperative pathological section (H&E stain, ×400), displaying alveolar spaces filled with foamy macrophages (indicated by arrow), and extensive infiltration of lymphocytes and plasma cells, which form lymphoid follicles in the bronchial wall and alveolar septa. E High-power view (GMS stain, ×400) revealing a small focus of Aspergillus hyphae (indicated by the arrow) within an alveolus

During the postoperative follow-up period, the patient remained disease-free with no radiological evidence of recurrence.

Discussion

As summarized in Table 1, all six patients in our series were strongly suspected of having lung cancer prior to surgery. This underscores the capacity of LP to mimic malignancy clinically and radiologically.

Table 1.

Summary of Clinicopathological Features of Six Patients with Lipoid Pneumonia

Case	Age/Sex	Clinical Presentation	Imaging Features	Tumor Markers	Preoperative Suspicion	Pathological Diagnosis
1	41/F	Asymptomatic, anxiety	Persistent Ground-Glass Opacity with a cyst in the right lower lobe	Normal	Indolent adenocarcinoma	Lipoid pneumonia
2	27/F	Asymptomatic	Cavitary nodule in the right middle lobe	Normal	Neoplasm / Granuloma	Endogenous (cholesterol) lipoid pneumonia
3	56/F	Discovered during trauma scan	Subsolid patchy opacity in the right lower lobe.	Normal	Invasive adenocarcinoma	Lipoid pneumonia
4	71/M	Cough, sputum, chest pain	Multiloculated cystic nodule in the left lower lobe	Normal	High-risk nodule / Neoplasm	Lipoid pneumonia with organizing pneumonia
5	34/M	Intermittent hemoptysis	Mass with spiculated margins in the right upper lobe.	NSE elevated (18.17 ng/ml)	Inflammatory granuloma / Neoplasm	Lipoid pneumonia with abscess
6	64/F	Discovered during health check-up	Large mass (76 mm) in the right upper lobe.	CEA elevated (21.1 ng/ml)	Lung cancer	Lipoid pneumonia

The diagnostic challenges posed by clinical and imaging findings

This series of six cases fully demonstrates the characteristic of LP as a “great mimicker” of lung cancer.

Clinical presentations were nonspecific, ranging from asymptomatic incidental findings to chronic cough and hemoptysis, consistent with previous reports.This is consistent with literature reports that patients with chronic LP are often asymptomatic or have mild symptoms, and are frequently diagnosed due to incidental findings on imaging during health check-ups, lacking any specific features [1].

Deceptive Imaging Features: CT is the primary imaging modality for LP.Its characteristic sign is the detection of fat density (-30 to -150 HU) within a consolidation or mass lesion [2]. However, as demonstrated in our series, the incidence of this key feature is low, and the preoperative CT reports of all six cases in this series did not suggest the presence of fat density. The lesion morphologies were highly deceptive, including a multiloculated cystic nodule mimicking a cystic adenocarcinoma (Case 3), sub-solid and ground-glass opacities indistinguishable from adenocarcinoma in situ or invasive adenocarcinoma (Cases 1, 2), and irregular masses with spiculated margins suggesting advanced cancer (Cases 4, 5), all of which are common features of lung adenocarcinoma. Especially in Case 6, the presentation as a giant mass with distal bronchial obstruction is extremely difficult to differentiate from central lung cancer on imaging. Studies have shown that only a few ELP patients have identifiable fat density on CT images. When complicated by severe inflammation, organization, or fibrosis, inflammatory changes may increase lesion density and obscure underlying fat [3].

Interference from tumor markers

In this series, Case 6 exhibited a persistently and significantly elevated CEA level (> 20 ng/ml), and Case 3 also presented with a slightly elevated NSE level. Although tumor markers are indicative for the diagnosis of lung cancer, false-positive elevations can also occur in inflammatory diseases. In this series, elevated tumor markers were observed in two patients: Case 6 had a persistently elevated CEA level (21.1 ng/mL) and Case 5’s NSE level was elevated at 18.17 ng/ml. The elevation of tumor markers in benign inflammatory diseases is a well-documented phenomenon, with underlying mechanisms linked to inflammation-driven tissue injury and repair. In the context of LP, persistent alveolar epithelial injury can induce the proliferation of type II pneumocytes, subsequently leading to increased synthesis and secretion of glycoproteins such as carcinoembryonic antigen (CEA) [4]. Furthermore, alveolar macrophages, the central cellular players in the pathology of LP, are also implicated. Additionally, the lipid-rich and protein-rich environment of the alveolar space may impair the clearance of CEA by macrophages, thereby indirectly increasing its serum concentration [5]. This pathophysiology is consistent with findings in other benign lung diseases, such as drug-induced pneumonia and pulmonary alveolar proteinosis, where inflammation and macrophage dysfunction also lead to marker elevation [6].

Therefore, elevated CEA and NSE levels in LP should be interpreted as nonspecific markers of inflammation and tissue remodeling rather than definitive evidence of malignancy. This exacerbates the clinical decision-making dilemma, making surgical exploration almost a necessary means of definitive diagnosis in some cases.

The central role and challenges in pathological diagnosis

Given the nonspecificity of clinical and imaging findings, pathological examination is the “gold standard” for diagnosing LP. All six patients in this series were ultimately diagnosed through paraffin-embedded pathology after surgical resection.

Typical Pathological Features: The core histological feature of LP is the presence of a large number of foamy macrophages (lipid-laden macrophages) aggregated within the alveolar spaces. Additionally, it is frequently accompanied by the infiltration of lymphocytes and plasma cells, the formation of lymphoid follicles, and varying degrees of interstitial fibrous tissue proliferation. In some instances, needle-shaped cholesterol clefts and foreign body giant cell reactions may also be observed. The pathology reports of all six cases in this series clearly described one or more of these typical features.

Diagnostic Challenges: Intraoperative frozen section pathology and biopsy have their limitations in diagnosis. This highlights a significant challenge in the diagnostic process: due to the heterogeneous distribution of inflammation and lipid deposits, small samples from needle biopsies may be subject to sampling bias. A biopsy might inadvertently sample an area of reactive atypical hyperplasia, as observed in our Case 3, leading to a false suspicion of malignancy, while overlooking diagnostic lipid-laden macrophages [7]. We must acknowledge that for junior pathologists or those less familiar with rare inflammatory conditions, the cellular atypia and architectural remodeling seen in reactive processes can closely mimic early-stage adenocarcinoma. This underscores the necessity of a more cautious evaluation of biopsy specimens and suggests that a second opinion from a senior subspecialist pathologist should be sought when confronted with such diagnostic ambiguity. A definitive diagnosis ultimately depends on adequate sampling and a detailed examination of the surgical resection specimen.

Our case series highlights that Endogenous Lipoid Pneumonia is often secondary to underlying pathology. Notably, special stains in Case 5 and Case 6 revealed occult fungal infections (Aspergillus) that were not apparent on initial imaging. This suggests that the ‘tumor-like’ mass was a result of the inflammatory response to the fungal pathogen, causing bronchial obstruction and subsequent lipid accumulation. This reinforces the importance of performing fungal stains (PAS, GMS) in suspected LP cases, even when malignancy is the primary concern.

Clinical management: diagnostic and therapeutic strategies

The diagnostic and therapeutic journey for patients with LP is complex. This case series offers several key insights into effective clinical management.

Broadening the diagnostic aperture

In clinical practice, when encountering solitary pulmonary nodules or masses, particularly those with atypical morphology, a poor response to anti-infective treatment, or only mildly to moderately elevated tumor markers, in addition to considering lung cancer, LP should also be included in the differential diagnosis, as this is a rare disease.

Although there was no clear history of exogenous lipid aspiration in this case series, in clinical practice, one should still patiently and meticulously inquire about the patient’s history of long-term use of liquid paraffin, oily nasal drops, lubricants, and any special occupational or lifestyle habits (e.g., “fire-eating,” vaping). The rarity of an ELP diagnosis is surprising, given the widespread use of lipid-containing substances and the high prevalence of conditions that promote their entry into the lungs [8]. This may be due to a significant underdiagnosis of ELP, or it might indicate that with any given exposure, certain individuals are prone to developing ELP, while others are not. The latter hypothesis is supported by the existence of some rare but well-documented cases of ELP secondary to commonly consumed lipid-containing substances, such as milk, egg yolk, vegetable oil, and cooking oil [9, 10]. We speculate that these inconspicuous substances are responsible for the ELP in patients from the present study who had no specific exposure to explain their condition.

The role of advanced imaging and Multi-Disciplinary Team (MDT) collaboration

Radiologists and clinicians should remain vigilant for low-density (fat) areas within suspicious lesions. The characteristic signal of fat on various MRI sequences can assist in confirming the presence of lipid. This includes high signal on T1-weighted images with corresponding signal loss on fat-suppressed sequences, and most specifically, signal loss on out-of-phase sequences compared to in-phase sequences in chemical shift imaging [11]. For a case that appears highly suspicious on imaging but cannot be confirmed through minimally invasive biopsy, the MDT model can integrate the expertise of specialists from multiple disciplines for a comprehensive evaluation. This approach helps circumvent the limitations of single-department decision-making and may decrease the incidence of unnecessary surgeries.

Principles of Treatment and the value of surgery

The primary treatment for LP is the elimination of exposure to the suspected lipid, which forms the basis of therapy [12]. For patients experiencing severe symptoms, extensive inflammation, or acute respiratory distress, corticosteroids are regarded as an effective treatment option [13]. In specific cases, such as when there are co-existing conditions similar to pulmonary alveolar proteinosis, whole-lung high-volume lavage has also been applied successfully [14].

All cases in this series underwent surgical resection, which served as both a diagnostic and therapeutic measure.

While wedge resection with intraoperative frozen section is the preferred approach for peripheral indeterminate nodules, lobectomy was deemed necessary in selected cases in our series. For instance, in Case 6, the lesion was central, large (> 7 cm), and involved the bronchus, anatomically precluding limited resection. In other cases, intraoperative frozen sections were ambiguous (indicating ‘inflammation suspicious for malignancy’ or ‘atypical hyperplasia’), prompting the surgical team to proceed with lobectomy to ensure complete removal of a potentially malignant lesion and to clear the source of chronic infection/obstruction. This underscores the dilemma surgeons face when LP perfectly mimics lung cancer intraoperatively. However, for indeterminate pulmonary nodules where lipoid pneumonia is a differential consideration, we advocate for the utilization of intraoperative frozen section analysis. If a wedge resection with frozen section pathology can confirm the presence of lipid-laden macrophages and exclude malignancy, the surgeon can confidently avoid a complete lobectomy.

Prognosis and Follow-up

Understanding the prognosis of LP is crucial. While surgical resection of a localized lesion, as demonstrated in our series, can be curative, the natural progression of diffuse or multifocal LP is unpredictable. It is crucial to recognize that even after the presumed causative agent has been identified and removed, clinical and radiological progression may continue. A study indicated that over a median follow-up period of one year, only 33% of patients showed radiological improvement, while 39% experienced deterioration [3]. This could be attributed to the persistence of lipid deposits that provoke a continuous inflammatory response. This underscores the significance of long-term follow-up, even in diagnosed cases, to monitor for disease progression or secondary complications.

Limitations

This study has several limitations. First, as a retrospective case series from a single institution with a small sample size (n = 6), the generalizability of our findings is limited. Second, given the retrospective nature of data collection, there may be recall bias regarding the patients’ history of lipid exposure, potentially obscuring the etiology in some cases. Third, our study only included patients who underwent surgical resection and had histopathologically confirmed diagnoses, therefore, the true prevalence of lipoid pneumonia in the general population is likely underestimated, as cases managed conservatively were excluded. Finally, long-term follow-up data was not available for some patients, limiting our assessment of the long-term prognosis of this condition. Despite these limitations, this series highlights critical diagnostic pitfalls and underscores the importance of maintaining a high index of suspicion for this rare entity.

Conclusion

Lipoid pneumonia remains a significant mimicker of lung cancer. Its nonspecific clinical and radiological features, coupled with potential tumor marker elevation, pose diagnostic challenges. Pathological examination is essential for definitive diagnosis. Clinicians should consider LP in the differential diagnosis of indeterminate pulmonary nodules, even in the absence of overt lipid exposure.

Authors contributions

X.L. (Xiaotong Lin) and X.L. (Xiangling Lin) wrote the main manuscript text and literature review; Y.Y(Yin Yin), H.L. (Hongsen Liang) and T.B. (Ting Bao) contributed to case collection, analyzed the clinical data , and preparation of figures and tables; Z.Y.(Zheng Yang) and Y.L. (Yun Li), as the corresponding author, supervised the study, coordinated the research, and critically reviewed and edited the manuscript. All authors reviewed and approved the final version of the manuscript.

Data availability

The data that support the findings of this study are not openly available due to ethical and privacy restrictions, as they contain information that could compromise patient confidentiality. The data are derived from the patients’ medical records and post-operative examination results. Requests for data access may be considered by the corresponding author upon reasonable request and subject to permission from the institution’s ethics committee.

Declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the Seventh Affiliated Hospital of Sun Yat-Sen University. Written informed consent for the use of clinical data was obtained from all patients at the time of admission.

Consent for publication

Written informed consent for publication was obtained from all participants.

Competing interests

The authors declare no competing interests.