This previously healthy 65-year-old man presented with fever, dyspnea, pleuritic chest pain, hemoptysis, presence of constitutional symptoms, tachycardia, lung consolidations, bronchiectasis, and elevated levels of inflammatory markers. The elevated levels of inflammatory markers, including the erythrocyte sedimentation rate and levels of C-reactive protein, are nonspecific findings.
A. Cancer
Considering the constellation of symptoms presented by the 65-year-old male patient, along with radiological findings and relevant history, the probability of lung cancer must be carefully assessed. The patient's chief complaints include hemoptysis, fever, pleuritic chest pain, and weight loss. These symptoms, when observed together, raise significant concern for an underlying malignancy, particularly lung cancer. Hemoptysis, although not pathognomonic for lung cancer, is a concerning symptom often associated with malignancies of the lung parenchyma (1).
The CT scan revealed consolidations in the pulmonary parenchyma. Consolidations, especially when multifocal or persistent, are concerning for neoplastic processes such as lung cancer (2). While consolidations can be seen in various pulmonary conditions, including infectious etiologies like pneumonia, the presence of consolidations in conjunction with the patient's symptoms and history warrants thorough investigation for malignancy.
Of significant relevance is the patient's history of cigarette smoking. Cigarette smoking is the most significant risk factor for the development of lung cancer, accounting for most cases.
Considering the patient's presentation of hemoptysis, fever, pleuritic chest pain, weight loss, consolidations on imaging, and a history of cigarette smoking, the probability of lung cancer is notably elevated. There are two primary types of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) (3). NSCLC is further categorized into three subtypes: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma (4). Adenocarcinoma is the most common form of lung cancer, particularly among smokers (4). It tends to occur in the outer regions of the lungs and is associated with a higher incidence in individuals with a history of smoking. Adenocarcinoma often presents with symptoms such as hemoptysis, cough, and weight loss (5).
B. Infectious diseases
Considering the clinical presentation, radiological findings, and regional epidemiology, the probability of infectious diseases such as tuberculosis (TB) and aspergillosis must be carefully considered.
1. Tuberculosis
Iran is considered a high-burden country for tuberculosis, with a notable incidence rate. The endemicity of TB in this region increases the pretest probability of the disease in patients presenting with compatible symptoms and radiological findings (6). Sputum smear microscopy and culture are commonly used for the diagnosis of pulmonary TB. However, it's essential to recognize the limitations of these tests (7, 8).
Smear microscopy has a sensitivity ranging from 36.9–55.6% and specificity of around 99%, while culture has higher sensitivity (approximately 80–90%) but takes longer for results (9, 10). Importantly, negative smear and culture results do not exclude the diagnosis of TB, especially in cases of paucibacillary disease or extrapulmonary involvement (10).
2. Aspergillosis
Although less common than tuberculosis, aspergillosis should also be considered in the differential diagnosis, particularly in immunocompromised individuals. Patients with aspergillosis may present with symptoms like TB, including hemoptysis, fever, and weight loss (11).
Tuberculosis and aspergillosis should emerge as significant considerations. The high prevalence of TB in Iran, along with the clinical and radiological findings, warrants thorough diagnostic evaluation, including sputum smear microscopy, culture, and potentially imaging-guided biopsy (12). It's crucial to recognize the limitations of diagnostic tests and maintain a high index of suspicion, especially in regions endemic for tuberculosis.
C. Pneumonia
Pneumonia typically presents with an acute onset of symptoms, including fever, cough, dyspnea, pleuritic chest pain, and constitutional symptoms like malaise and weight loss (13). However, in this case, the clinical manifestation began three months ago, suggesting a chronic or indolent process rather than an acute infectious etiology. While the presence of consolidations on CT scan is consistent with pneumonia, chronic pneumonia is less common and typically presents with more subtle radiological findings, such as persistent infiltrates or fibrotic changes (13, 14).
Given the chronicity of symptoms and the need to explore alternative diagnoses, further diagnostic evaluation beyond typical pneumonia workup may be warranted. This may include pulmonary function tests, autoimmune serology, imaging studies to assess for structural lung disease or malignancy, and possibly bronchoscopy with biopsy to obtain tissue for histopathological examination.
While pneumonia remains a consideration in the differential diagnosis, its probability is diminished by the chronic nature of the patient's symptoms over the past three months.
D. Interstitial lung disease (ILD)
ILD encompasses a diverse group of disorders characterized by inflammation and fibrosis of the lung parenchyma, resulting in progressive dyspnea, cough, and impaired gas exchange. Patients may present with constitutional symptoms such as fever and weight loss, particularly in cases of more aggressive or advanced disease. Hemoptysis can occur in ILD, though it is less common compared to other pulmonary conditions (15).
On imaging, ILD typically manifests as reticular opacities, ground-glass opacities, or honeycombing on CT scan, reflecting interstitial inflammation and fibrosis. Consolidations may also be present, particularly in cases of acute exacerbation or superimposed infection (16).
The presence of chronic symptoms such as hemoptysis, fever, pleuritic chest pain, and weight loss, in conjunction with radiological evidence of consolidations and other interstitial changes, raises suspicion for underlying ILD. The chronicity and progressive nature of the symptoms over time are consistent with the natural history of ILD, which often presents insidiously and worsens gradually (15).
Diagnosis of ILD typically involves a combination of clinical assessment, high-resolution CT imaging, pulmonary function tests, and sometimes, biopsy for histopathological evaluation. In the context of chronic symptoms such as hemoptysis, fever, pleuritic chest pain, weight loss, and pulmonary consolidations, interstitial lung disease (ILD) emerges as a significant consideration (17).
E. Pulmonary vasculitis
In the evaluation of the patient, consideration must be given to pulmonary vasculitis, particularly Wegener's granulomatosis too. Wegener's granulomatosis is a systemic autoimmune disorder characterized by necrotizing granulomatous inflammation of the respiratory tract, systemic vasculitis, and glomerulonephritis. Patients may present with constitutional symptoms such as fever, weight loss, and malaise, along with respiratory symptoms including hemoptysis, cough, and pleuritic chest pain. The triad of upper respiratory tract involvement (such as sinusitis), lower respiratory tract involvement (such as hemoptysis and pulmonary infiltrates), and glomerulonephritis constitutes the classic presentation of Wegener's granulomatosis (18).
On imaging, pulmonary vasculitis, including Wegener's granulomatosis, can manifest as multiple nodular opacities, ground-glass opacities, or consolidations. These findings may be bilateral and involve multiple lung lobes (19).
Diagnosis of Wegener's granulomatosis typically involves a combination of clinical assessment, serological testing (such as anti-neutrophil cytoplasmic antibodies, or ANCA), imaging studies, and tissue biopsy. ANCA testing, specifically anti-proteinase 3 (PR3) antibodies, may be positive in up to 80% of cases, aiding in the diagnosis. Tissue biopsy, often obtained via bronchoscopy or surgical lung biopsy, is crucial for confirming the presence of granulomatous inflammation and vasculitis (20).
A comprehensive diagnostic approach, including serological testing and tissue biopsy, is essential for accurate diagnosis and appropriate management of this potentially life-threatening condition.