Title : Spindle cell carcinoma of the lung masquerading as pulmonary aspergillosis: A diagnostic challenge
Abstract:
Pulmonary spindle cell carcinoma (SpCC) is an exceptionally rare and highly aggressive subtype of pulmonary sarcomatoid carcinoma, accounting for approximately 0.4% of primary lung malignancies. Diagnosis is often challenging because its clinical, radiologic, and even initial histopathologic features may mimic benign or infectious pulmonary diseases, leading to delayed recognition.
Introduction: Pulmonary spindle cell carcinoma (SpCC) is an exceptionally rare and highly aggressive subtype of pulmonary sarcomatoid carcinoma, representing approximately 0.4% of primary lung malignancies. Because of its rarity, the clinicopathologic characteristics and optimal management of this tumor remain poorly defined, and no standardized treatment guidelines currently exist. Patients often present with nonspecific respiratory symptoms, while radiologic findings frequently overlap with those of infectious, inflammatory, or other malignant pulmonary diseases. Furthermore, small biopsy specimens and cytologic samples may be nondiagnostic because of the tumor's marked histologic heterogeneity. Consequently, immunohistochemical evaluation is often required to establish a definitive diagnosis. We report a case of pulmonary spindle cell carcinoma that initially mimicked pulmonary infection, resulting in delayed diagnosis despite extensive initial evaluation.
Case Presentation: A 76-year-old male presented with a two-month history of non-productive cough, without associated hemoptysis. Initial chest radiography revealed a right paratracheal/suprahilar soft tissue density. Subsequent contrast-enhanced chest computed tomography (CT) scan demonstrated a well-defined, heterogeneously enhancing mass lesion with internal areas of hypodensity in the right apical region, measuring 4.4 × 4.1 × 3.6 cm. Biopsy of the lesion showed lung parenchyma with patchy chronic interstitial inflammation, intraalveolar fibrin deposition, organizing pneumonia, and atypical pneumocyte hyperplasia, favoring a reactive process. Cytological analysis of the BAL fluid demonstrated atypical cells, negative for malignancy, composed predominantly of bronchial epithelial cells admixed with lymphocytes and histiocytes within a background of blood and fibrin. The Aspergillus galactomannan antigen test was positive (patient index: 4.89; positive ≥ 0.50), while Mycobacterium tuberculosis (MTB) PCR was negative. Based on these findings, the patient was then managed as a case of pulmonary aspergilloma and was started on antifungal therapy with isavuconazonium sulfate. Two months later, he developed progressive hoarseness without dysphagia, aspiration, or dyspnea. Follow-up chest CT performed three months after the initial study demonstrated marked interval enlargement of the right apical mass, now measuring 8.8 × 9.2 × 8.1 cm, with extension into the anterior and posterior segments of the right upper lobe. PET CT scan demonstrated persistent heterogeneous FDG avidity (SUV max 20.5) within the lesion, which measured 9.3 × 9.2 × 8.1 cm. The mass remained centered in the right apical region, abutting the right paratracheal space and producing significant mass effect with leftward mediastinal deviation. Incidentally, right internal jugular vein thrombosis was identified, prompting hospital admission. During the admission, repeat CT-guided core needle biopsy of the lung mass and ultrasound-guided thoracentesis were performed. Thoracentesis yielded 250 mL of clear yellow pleural fluid. Pleural fluid cytology demonstrated atypical cells, while MTB PCR remained negative. Histopathologic examination of the repeat biopsy confirmed spindle cell carcinoma. Immunohistochemistry demonstrated PD-L1 expression >90%, focal CAM5.2 positivity, focal p40 positivity, and negativity for CK, TTF-1, and SOX10, supporting the diagnosis of pulmonary spindle cell carcinoma. The patient was then referred to radiation oncology and received 10 fractions of radiation therapy.
Discussion: Sarcomatoid carcinoma of the lung is an uncommon, high-grade, poorly differentiated subtype of non-small cell lung cancer. The incidence of sarcoma accounts for approximately 0.3% to 1.3% of all lung cancer cases. The World Health Organization (WHO) classifies sarcomatoid carcinoma into five primary subtypes based on histological characteristics: spindle cell carcinoma, pleomorphic carcinoma, carcinosarcoma, giant cell carcinoma, and pulmonary blastoma. Pulmonary spindle cell carcinoma consists of a pure population of spindle cells, which frequently involves the periphery of the lung and consists of spindle-shaped tumor cells. Pulmonary spindle cell carcinoma typically presents with cough and hemoptysis, occurring in nearly 50% of cases involving proximal tumors. In some patients, the bronchial obstruction caused by cancer results in recurrent pneumonia and progressive breathlessness. The disease often follows an aggressive course, associated with a poor prognosis and a five-year survival rate of about 20%. Histopathological diagnosis is essential for the characterization and classification of these tumors due to their high cellular pleomorphism. Spindle cell carcinoma (SPCC) displays histological features of both epithelial and mesenchymal tumors. Clinically, it usually presents with nonspecific symptoms and imaging findings that resemble other types of lung cancer, making immunohistochemistry critical for establishing a definitive diagnosis. Spindle cell carcinoma is known to exhibit a more aggressive clinical course compared to other types of malignant lung cancers. Additionally, its response to chemotherapy and radiation therapy is typically poor. However, some reports and studies suggest that carboplatin-based chemotherapy combined with surgical resection may offer an effective treatment approach for this carcinoma.
Conclusion: Pulmonary spindle cell carcinoma remains a rare and highly aggressive variant of nonsmall cell lung carcinoma, characterized by poor differentiation, rapid progression, and limited therapeutic responsiveness. This case illustrates the diagnostic pitfalls of pulmonary spindle cell carcinoma, which may initially masquerade as pulmonary infection and remain undetected despite negative cytology and nondiagnostic biopsy findings. Rapid radiologic progression despite appropriate antimicrobial therapy should prompt reconsideration of the diagnosis and repeat tissue sampling. Persistent clinical suspicion, multidisciplinary evaluation, and adequate histopathologic assessment with immunohistochemistry are essential for the timely diagnosis of this rare and aggressive malignancy. Given the tumor’s aggressive behavior, poor response to conventional therapies, and lack of standardized treatment protocols, this case emphasizes the need for heightened clinical suspicion, multidisciplinary management, and further research to optimize diagnostic accuracy and therapeutic outcomes in spindle cell carcinoma of the lung.
