A case report of pulmonary granuloma misdiagnosed as a malignant tumor

Abstract

The objective of this study was to investigate the clinical characteristics and underlying causes of misdiagnosis in pulmonary granulomas, analyze the diagnostic challenges and differential diagnostic process, and improve clinical understanding in order to reduce misdiagnosis and optimize treatment. A retrospective analysis was conducted on a clinical case of pulmonary granuloma in a patient presenting with cough, sputum production, and hemoptysis. Initial computed tomography imaging revealed a malignant lung tumor. However, trans-thoracoscopy indicated that the lesion was an inflammatory granuloma, and the final diagnosis confirmed this finding. This case emphasizes that symptoms such as cough, sputum production, and hemoptysis may be indicative of pulmonary granulomas and may be misdiagnosed as malignant lung tumors. Therefore, a systematic and comprehensive diagnostic approach is essential. The integration of medical history, physical examination, and auxiliary tests, particularly pathological evaluation supported by positron emission tomography/computed tomography, can significantly reduce the risk of misdiagnosis, promote timely intervention, and improve the patient’s prognosis.

Introduction

Granulomas are nodular lesions formed by the aggregation of macrophages and their derivatives, including epithelioid and multinucleated giant cells, in response to delayed-type hypersensitivity. ¹ These lesions can be triggered by a variety of causes, such as infections (e.g., tuberculosis), foreign bodies, autoimmune diseases, and allergic reactions. ² Granulomas are classified into infectious and noninfectious types, with characteristic histological features depending on the underlying cause. ³

Infectious granulomas are caused by pathogens such as Mycobacterium tuberculosis, fungi, and parasites, with tuberculosis presenting classic tuberculous granulomas featuring caseous necrosis and surrounding lymphocytic infiltration. ⁴ Noninfectious granulomas, such as those found in patients with sarcoidosis, are typically nonnecrotizing and consist mainly of epithelioid cells and multinucleated giant cells. ⁵

Granulomas can mimic malignant tumors, complicating diagnosis. For example, a granulomatous lesion may be misdiagnosed as lung cancer, which is characterized by nonspecific symptoms such as coughing, blood in sputum, and chest pain. ⁶ Diagnosis of lung cancer involves imaging techniques, including computed tomography (CT) and positron emission tomography (PET), and histopathological examination. Case of granulomatous inflammation initially misdiagnosed as lung cancer underscore the importance of distinguishing between these conditions to ensure appropriate management. ⁷

The differential diagnosis between pulmonary granuloma and lung cancer can be challenging because of their similar radiological features. Granulomas often appear as nodular lesions on imaging, which may overlap with the appearance of primary lung malignancies, particularly in patients with sarcoidosis or tuberculosis. ⁸ However, granulomas typically lack the aggressive features observed in malignancies, such as irregular margins, rapid growth, or lymph node metastasis. ⁹ In contrast, lung cancer is often associated with a history of smoking, positive tumor markers, and signs of local invasion or distant metastasis. ¹⁰ Imaging modalities, such as contrast-enhanced CT and PET/CT, and, when necessary, biopsy are essential for accurate diagnosis. Early differentiation is critical to avoid misdiagnosis and ensure appropriate treatment, as granulomas are benign and may resolve with conservative management, whereas lung cancer requires oncologic intervention.

This study aimed to investigate the clinical characteristics and causes of misdiagnosis of pulmonary granuloma, analyze the associated diagnostic challenges and differential diagnosis, and enhance clinical understanding to reduce misdiagnosis. A retrospective analysis was conducted on a clinical case of pulmonary granuloma in a patient with cough, sputum production, and hemoptysis. Initial CT imaging suggested a malignant lung tumor.

Case history/examination

A man in his early 60s presented to the Department of Oncology at The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine on 3 December 2024. The patient reported a 2-month history of cough and sputum production with intermittent hemoptysis. At the beginning of 2024, he experienced cough with sputum, a small amount of blood in the sputum, and intermittent chest pain. At that time, the patient had no chills, fever, palpitations, chest tightness, dizziness, headache, hot flashes, night sweats, nausea, or vomiting. The patient did not seek medical care for these symptoms. Although the patient later underwent systematic diagnosis and treatment, the symptoms recurred. On 28 November 2024, a chest CT scan performed at Guizhou Province Qiandongnan Prefecture People’s Hospital revealed a lesion in the anterior segment of the upper lobe of the left lung measuring approximately 34 mm × 24 mm (Figure 1). In November 2024, the patient underwent contrast-enhanced chest CT at The Second Affiliated Hospital of Guizhou Medical University. The report indicated a space-occupying lesion in the upper lobe of the left lung with mild surrounding inflammation. The lesion measured approximately 28 mm × 20 mm × 21 mm, and lung cancer was suspected (Figure 2). Therefore, fiberoptic bronchoscopy was recommended. Subsequently, the patient was referred to The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine. The patient experienced no significant weight loss in the past 6 months. Upon admission, the patient reported irritability. He presented with mild cough with scant white sputum but no hemoptysis or chest pain. The patient reported no symptoms such as chills or fever, dizziness, headache, palpitations, or chest tightness. He reported poor sleep but had normal bowel and urinary function. The reporting of this study conforms to Case Report (CARE) guidelines. ¹¹ The patient provided written informed consent and consented to the publication of his data in this research.

Figure 1.

Chest computed tomography scan.

Figure 2.

Contrast-enhanced chest computed tomography.

Medical history and health status

The patient had a history of alcohol consumption and smoking (approximately 20 cigarettes per day) for more than 30 years. There was no family history of any infectious or genetic diseases. Physical examination revealed a height of 160 cm, weight of 61 kg, and Karnofsky performance status score of 100. The patient was conscious, well developed, well nourished, and not in acute distress. No jaundice of the skin or sclera was observed, and the lips were rosy. No enlargement or tenderness of the superficial lymph nodes was observed. The patient appeared normal with no deformities. The eyes were symmetrical, the conjunctiva was not icteric or congested, and the pupils were equal and round. The thyroid was normal, the trachea was midline, and no jugular venous distension was observed. The chest was symmetrical without deformities. The respiratory rhythm was regular, and the intercostal spaces were normal. Percussion of both lungs was clear, and diaphragmatic excursion was normal. Breath sounds were clear, and no rales or pleural friction rubs were detected. The precordium showed no abnormal bulging or retraction, and no abnormal apical impulse was detected. The heart rate was 80 beats/min with a regular rhythm. Heart sounds were normal, and no murmurs were detected during valve auscultation. The abdomen was flat and soft with normal abdominal respiration. The umbilicus was normal, and no abdominal wall varicose veins were observed. No tenderness, rebound tenderness, muscle guarding, fluid wave, or masses were detected. The liver and spleen were not palpable, and no hepatomegaly or splenomegaly was observed. Renal angle tenderness was not observed. The liver percussion border was normal, with the upper margin at the fifth right intercostal space. Murphy’s sign was negative. Bowel sounds were normal (approximately 4/min), and no vascular bruits were heard. The spine was normal without deformities, and the limbs showed no deformity or edema, with a normal range of motion. Physiological reflexes were present bilaterally, and no pathological reflexes were elicited.

Diagnosis and treatment

Routine laboratory examinations were performed after admission. No abnormalities were observed in liver function, renal function, or electrolyte levels. Blood tests revealed a leukocyte count of 10.32 × 10⁹/L and an absolute neutrophil count of 7.29 × 10⁹/L. PET/CT revealed several abnormalities. In the anterior segment of the upper lobe of the left lung, a nodule with irregular soft tissue density showed increased fluorodeoxyglucose (FDG) metabolism, resulting in a differential diagnosis that included inflammatory granuloma. In contrast, the basal segment of the lower lobe of the left lung showed nodularity with irregular ground-glass density and no increase in FDG metabolism, suggesting atypical adenomatous hyperplasia. Additionally, flocculent ground-glass density shadows in the apical segment of the right upper lobe and the anterior basal segment of the lower lobe also exhibited no increase in FDG metabolism, which was considered consistent with chronic inflammation. Additionally, multiple micronodules were observed in both lungs, with no increase in FDG metabolism, which were considered consistent with proliferative foci. Further findings included multiple pulmonary vesicles in the upper lobes of both lungs and the lower lobe of the left lung. Multiple lymph nodes in the bilateral neck and submandibular regions (IB, IIA, IIB, III, and VA) showed no increase in FDG metabolism and were considered consistent with reactive hyperplasia. Other findings included left liver lobe atrophy with a benign lesion (likely a hemangioma); a left renal cyst; prostate hyperplasia and calcification; and degenerative changes in the cervical, thoracic, and lumbar spine. No abnormalities were observed in the head on FDG-PET imaging or CT scans. Following consultation with specialists in thoracic surgery, pulmonary internal medicine, cardiac internal medicine, and critical medical disciplines, bronchoscopy was recommended to elucidate the pathology and guide surgical treatment. Therefore, the preoperative evaluation was completed to rule out contraindications to surgery. On 12 December 2024, the patient underwent single-port thoracoscopic wedge resection of the left upper lung, pulmonary repair, and pleural adhesion release under general anesthesia (Figure 3). After surgery, the patient received symptomatic support, including intravenous cephalosporin sodium (1 g every 12 h for 5 days) for infection prevention, atomized atomium hydrochloride (2.5 mg via nebulizer every 6 h), ambroxol (30 mg orally 3 times daily) for expectoration, and dihydrocodeine (10 mg orally every 4–6 h as needed for pain relief). The surgical team ensured timely dressing changes and extubation, with regular follow-up assessments to monitor recovery and prevent complications. Intraoperative frozen pathology (C202416653) confirmed the presence of benign lesions characterized by various tissue morphologies, primarily inflammation with fibrous tissue hyperplasia, foam cell reaction, focal glass-like degeneration, organizing pneumonia, increased neutrophil infiltration, microabscess formation, and local granuloma structures. The final postoperative pathology report on 12 December 2024 reconfirmed these findings, revealing a benign lesion with inflammation, fibrous tissue hyperplasia, and local granuloma structures in the left upper lung (Figure 4). The patient’s wound healed well, and chest radiography revealed good lung re-expansion. The patient was discharged on 16 December 2024. A postdischarge chest CT (Figure 5) revealed the expected postresection changes in the anterior segment of the left upper lung and fibrotic foci in the lower lobes of the right lung.

Figure 3.

Intraoperative tissue resection.

Figure 4.

Postoperative histopathological results.

Figure 5.

Follow-up chest computer tomography scan after discharge.

Discussion

Pulmonary inflammatory granulomas are often misdiagnosed as malignant lung tumors because of their similar radiological appearance. In the present case, the initial chest CT suggested a malignant tumor, which resulted in further investigations. However, subsequent PET/CT imaging revealed findings consistent with an inflammatory granuloma, ultimately confirmed by postoperative pathology. This type of misdiagnosis is not uncommon, as granulomas, particularly in the lungs, can mimic malignant tumors on imaging. Conditions such as sarcoidosis and tuberculosis frequently present granulomatous lesions that closely resemble malignancies, particularly because of the nonspecific nature of imaging findings.^12,13 The ability of granulomas to exhibit increased FDG uptake on PET/CT further complicates differentiation, as FDG uptake is typically associated with malignant processes. ¹⁴ However, it is important to note that increased FDG uptake can also occur in benign inflammatory conditions, including granulomas, because of their active metabolic processes during inflammation. ¹⁵ This highlights the need for a comprehensive diagnostic approach that incorporates clinical history, imaging findings, and pathological evaluation.

In the present case, the patient, a middle-aged man with a significant smoking history, presented with a 2-month history of cough, sputum production, and intermittent hemoptysis. The initial chest CT raised concern for lung cancer, a common diagnosis in patients with a history of smoking. However, further imaging, including contrast-enhanced CT and PET/CT, indicated a differential diagnosis that included inflammatory granuloma, atypical adenomatous hyperplasia, chronic inflammation, and possible malignancy. This finding is consistent with those from previous studies showing that imaging findings alone may be insufficient in differentiating between benign and malignant pulmonary lesions. ¹⁶ The patient’s clinical presentation, together with the imaging findings, prompted a multidisciplinary team to recommend surgical resection, which ultimately confirmed the benign nature of the lesion. This approach is consistent with that of the existing literature, emphasizing the importance of a thorough diagnostic workup, particularly when imaging results are inconclusive or suggest possible malignancy. ¹⁷

The potential etiologies of granulomas, which can arise from infectious, foreign body-related, or autoimmune causes, were also considered in this case. Although the specific etiology of the granuloma in this patient remained unidentified, granulomas can result from a variety of factors. Infectious agents such as M. tuberculosis and fungi are known to cause granulomatous inflammation, whereas foreign bodies or autoimmune diseases such as sarcoidosis can also result in granuloma formation. ¹⁸ The patient’s smoking history increased the possibility of chronic inflammation or underlying infectious or environmental exposure as contributing factors. In fact, smoking is known to increase the likelihood of chronic lung diseases, including those that may cause granulomatous inflammation. ¹⁹

A critical aspect of this case is the importance of distinguishing between benign and malignant lesions, particularly in high-risk individuals such as patients with a history of smoking. As demonstrated in the literature, lung cancer is frequently characterized by aggressive imaging features, such as irregular margins, rapid growth, or lymph node involvement. ²⁰ In contrast, granulomas typically have more well-defined borders and lack these aggressive characteristics. Additionally, the absence of abnormal tumor markers and the presence of stable, nonprogressive lesions over time are important clinical features suggesting a benign etiology, as observed in this patient. ²¹

The role of postoperative surveillance cannot be overstated, particularly in cases with initially unclear diagnoses. As emphasized by Japuntich et al., ²² regular follow-up with imaging and clinical assessment is essential to monitor for potential malignancy, especially in patients with risk factors such as prolonged smoking. In this case, the patient’s uneventful recovery and subsequent imaging showed expected postresection changes, confirming the absence of malignancy. This finding highlights the importance of regular postoperative assessment to ensure timely intervention if malignancy were to develop.

Several limitations of this study should be considered. First, the precise etiology of the granuloma was not identified despite extensive diagnostic workup, including imaging and pathological evaluation. Although granulomas can result from various causes, such as infections, autoimmune conditions, or foreign body reactions, the inability to determine the underlying cause may limit a deeper understanding of the patient’s condition and could affect treatment decisions. Second, although the differentiation between benign and malignant lesions was based on imaging and pathological findings, reliance on a single diagnostic modality (i.e. PET/CT) represents a limitation. Although PET/CT is valuable for detecting metabolic activity, its ability to differentiate between benign and malignant lesions is limited, as FDG uptake can also occur in inflammatory conditions. Third, although the multidisciplinary approach in this case facilitated an accurate diagnosis, the availability and coordination of specialized care may not be achievable in all clinical settings, potentially affecting diagnostic accuracy in other environments. In addition, no long-term follow-up was reported in this case; therefore, it remains uncertain whether further imaging or assessments would be necessary to monitor for granuloma recurrence or the development of malignancy. Finally, although smoking is a well-established risk factor for lung cancer and chronic lung diseases, other potential environmental exposures or genetic factors were not explored in this case, limiting the generalizability of the findings to broader patient populations.

In conclusion, this case highlights the complexity of diagnosing lung lesions that may mimic malignancy, particularly in patients with a high risk of lung cancer. The integration of clinical, radiological, and pathological findings, together with a multidisciplinary approach, is essential to minimize misdiagnosis and ensure appropriate management. A thorough understanding of the potential etiologies of granulomas, the radiological features that differentiate benign and malignant lesions, and the role of FDG-PET imaging in inflammatory processes may aid in the accurate diagnosis and treatment of such cases.

Data availability statement

No new data were created or analyzed in this study.

Declaration of conflicting interests

The authors declare that there is no conflict of interest.

Ethics approval statement

Ethical approval for this study was obtained from the institutional ethics committee or the relevant ethics review board in accordance with the principles of the Declaration of Helsinki.

Funding statement

This work was supported by the Macao Key R&D Funding Program (Project Number: 0001/2024/AKP2) and the Macao University of Science and Technology Research Fund (Project Number: FRG-24-046-FC). The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Patient consent statement

Written informed consent was obtained from the patient.