Pulmonary aspergilloma (PA) is one of the five acknowledged clinicopathological forms of chronic pulmonary aspergillosis (CPA) [1],[2] and a frequent clinical presentation of lung infection caused by Aspergillus species. Its defining feature is the presence of a viable fungal mass inside a previously existing lung cavity. Usually, this mass is made up of fungal colonies, most notably A. fumigatus (in about 95% of cases), as well as inflammatory cells, fibrin, blood, and mucus [2],[3].

Pulmonary aspergilloma is slightly more common in males, with a median age of 65 years at diagnosis. Most patients lived either in farming areas or in large cities [4]. This condition is commonly associated with pre-existing pulmonary comorbidities, such as tuberculosis (reported in 25–80% of cases), chronic obstructive pulmonary disease (COPD), non-tuberculous mycobacterial infections (NTMB), bronchiectasis, sarcoidosis, lung abscesses, and necrotic lung cancer [3],[4],[5].

This report presents the case of a patient diagnosed with PA six months after surgical treatment for primary squamous cell lung carcinoma (SQCLC), although the radiographic appearance of a mass observed in the right lower lung lobe was most indicative of tumor relapse.

A 69-year-old patient, a former smoker, comes for a surgical examination, in order to assess the possibility of surgical treatment of histopathologically confirmed primary SQCLC. The patient reported a 5-month history of productive cough. His medical history included arterial hypertension, type 2 diabetes mellitus, and benign prostatic hyperplasia. He claimed that he had never experienced tuberculosis or any other respiratory comorbidities. Transbronchial biopsy tissue samples were histopathologically analyzed to determine the diagnosis of SQCLC. The patient had not undergone any neoadjuvant treatment. The chest X-ray (Figure 1) shows a soft tissue mass with an oval shape measuring up to 40 mm in diameter in the center right pulmonary field, next to the lateral chest wall. Contrast-enhanced CT of the chest (CECT) more precisely identified an excavated tumor with thickened walls and lobulated contours, situated in the upper lobe of the right lung, measuring 41×37×30 mm (Figure 2A and Figure 2B).

Following a thorough preoperative assessment and after obtaining informed consent from the patient, surgical intervention was carried out. Two months after the diagnosis, the patient had a right upper lobectomy using a uniportal thoracoscopic technique. On the fourth day following surgery, the patient was released after a smooth perioperative and postoperative course. According to the multidisciplinary tumor board’s advice, postoperative management included 3 cycles of adjuvant chemotherapy using cisplatin and etoposide. The resected lung tissue’s histopathological analysis revealed a primary SQCLC that was invasive and moderately differentiated. All dissected lymph nodes (interlobar, hilar, subcarinal, and lower paratracheal) had no metastases, and the surgical borders were clear (R0 resection). The tumor was classified as IB (pT2aN0Mx) in accordance with the 9th edition of the TNM classification for lung cancer [6].

Six months after surgery (three months after chemotherapy), a follow-up chest CECT scan revealed a recently formed oval lesion with spiculated borders in the superior segment (S6) of the ipsilateral right lower lobe, measuring 28×39×42 mm, as well as two neighboring nodules near the interlobar area (Figure 3A). The patient was then admitted to the Pulmonology Clinic for additional testing and therapy.

Fine-needle aspiration biopsy (FNAB) of the lesion excluded tumor recurrence, which had been the initial suspicion due to the lesion‘s radiographic features, and confirmed the presence of fungal elements in the lung tissue, consisting of granulation tissue and fungal colonies. Serologic testing supported the diagnosis of an Aspergillus infection (anti-Aspergillus IgM: 836 U/mL; IgG negative).

The patient was treated conservatively: initially with intravenous voriconazole (200 mg twice on the first day, followed by 200 mg once daily for 13 days), and continued with oral itraconazole (200 mg daily) for six weeks following discharge. Throughout hospitalization and treatment, the patient remained asymptomatic. Hematological parameters, including neutrophil and eosinophil counts, as well as standard biochemical markers such as C-reactive protein, plasma procalcitonin, IL-6, and erythrocyte sedimentation rate, remained within normal reference ranges.

Over a 15-month follow-up period, control CECT scans demonstrated complete resolution of the PA, with residual calcified fibrous tissue replacing the previously observed lesion (Figure 3B, Figure 3C, Figure 3D, Figure 3E, Figure 3F). Also, there were no signs of SQCLC recurrence.

Although tuberculosis and COPD are among the most common pulmonary conditions associated with the development of PA, recent studies have also identified lung cancer as an important etiopathogenetic factor. Several mechanisms have been proposed to explain the potential coexistence of these two diseases: (I) structural damage to the lung parenchyma caused by the malignant process (e.g., inflammation, ischemic necrosis); (II) surgical intervention itself (e.g., dead space, iatrogenic lung injury, prolonged air leak, bronchopleural fistula); and (III) post-radiation cavitation, among others [5],[7],[8],[9].

In patients with lung cancer, Shin et al. [7] found a 10-year incidence of PA of 3.5%. It is interesting to note that, in line with the current case, they discovered that patients who had surgery for SQCLC had a considerably higher incidence of PA (41.1% of cases) than those with other histological subtypes of lung cancer [7]. The histopathological features of SQCLC, such as its rapid growth rate, central ischemic necrosis, and resulting development of cavitary lesions, may account for this link [7],[10]. The development of PA may result from the secondary colonization of these cavitations by fungi.

Additional risk factors for PA in patients with lung cancer include male sex, smoking history, lower body mass index, immunosuppression, COPD, interstitial lung disease, thoracotomy (which carries a ninefold higher risk compared to thoracoscopic approaches), late postoperative complications (such as pneumonia or atelectasis), and concomitant chemoradiotherapy [5],[7],[8],[9].

The most common clinical manifestations of PA are fever, malaise, weight loss, productive cough, and hemoptysis, which can occasionally be massive and fatal [11]. However, PA can be present as an indolent form of aspergillosis, particularly in immunocompetent, asymptomatic patients, as seen in this case.

A combination of clinical presentation, radiological results, and laboratory tests, such as fungal cultures, serological testing, and histopathological analysis, is used to diagnose PA [11],[12]. The identification of anti-Aspergillus IgG antibodies in serum is indicative of PA, but their absence does not rule it out. According to a study by Zhu et al. [12], just 41.7% of PA patients had measurable anti-Aspergillus IgG antibodies.

Management of PA can be either surgical or conservative. In 7–10% of cases, spontaneous resolution has been documented [3]. Posterolateral thoracotomy with extrapleural dissection remains the standard open surgical approach, offering direct visualization of the lesion, controlled pleuro-pulmonary dissection, effective lung palpation, and prompt hemostasis [13],[14]. Lobectomy is generally considered the preferred extent of resection [7],[8],[15], although segmentectomy or wedge resection may be sufficient in asymptomatic patients with small (<3 cm), peripheral lesions [2],[4]. In our case, surgical intervention was not performed. Following consultation with a thoracic surgeon, antifungal therapy was initiated with voriconazole, followed by itraconazole. The patient responded well to the treatment, with complete radiological resolution of the lesion.

In terms of pharmacological therapy, the Infectious Diseases Society of America (IDSA) guidelines emphasize the usage of itraconazole and voriconazole as first-line drugs for PA [16]. Studies assessing the effectiveness of these two agents in CPA show that itraconazole has a clinical response rate of around 76.5% and voriconazole has a clinical response rate of around 61% [17],[18].

The prognosis of lung cancer in the context of PA is contingent upon a number of variables. According to Jiang et al. [1], older age, male sex, diabetes mellitus, and sublobar resection were all significantly linked to worse outcomes. Regarding PA, the retrospective study conducted by Bo-Guen Kim et al. [19] indicates that the development of CPA did not affect lung cancer mortality in the multivariable analysis.

Pulmonary aspergilloma and SQCLC share several risk factors, as well as overlapping clinical and radiological features. Given that PA can closely mimic primary SQCLC or its recurrence, both clinically and radiographically, this case underscores the importance of including PA in the differential diagnosis of new or recurrent pulmonary lesions—particularly in patients with aforementioned risk factors.

This case report may be of particular interest to infectious disease specialists, pulmonologists, thoracic surgeons, as well as general practitioners, medical residents, and students.