Sarcoid like reaction confounding the diagnosis of pulmonary adenocarcinoma

Introduction: Co-existing granulomatous inflammation in lung cancer has been reported. Sarcoidosis was also reported as an independent risk factor for development of lung cancer. We would like to report a case of multiple lung nodules showing non-caseating granulomas in initial needle biopsy and later showing adenocarcinoma in wedge biopsies. Case report: A 66 yr old female with smoking history found to have multiple spiculated lung nodules in low dose computed tomography scan. Three nodules in left upper lobe and one nodule in right upper lobe largest measuring 25 mm. Positron Emission Tomography scan showed hypermetabolic activity in all nodules highly suspicious for malignancy. Based on the Swensen/Mayo nodule malignancy risk calculator, the patient's lung cancer risk was estimated as 82%. Surprisingly needle biopsy of the left upper lobe 25mm nodule showed non-caseating granulomas and no malignant cells were seen. After ruling out all possible etiologies of granulomatous lung disease such as hypersensitivity pneumonitis, vasculitis, common variable immune deficiency, connective tissue disease, fungal and mycobacterium infections, patient was treated for sarcoidosis. Because of no improvement with steroids, patient underwent video-assisted thoracoscopic wedge biopsies of other two nodules in left upper lobe which showed moderately differentiated invasive adenocarcinoma with a predominant lepidic pattern along with coexisting granulomas. EGFR and ALK mutations were negative. She was treated carboplatin, pemetrexed and bevacizumab chemotherapy for stage IV lung adenocarcinoma (T1c, No, M1a) and had favorable response. Discussion: Granulomatous inflammation has been reported to be seen in tumor nodules and lymph nodes in some lung cancer cases. In a retrospective study based on Danish registry in 1973, sarcoidosis was associated with three fold increased incidence of bronchogenic cancer. The cancer incidence was higher in symptomatic sarcoidosis (1-5 times) patients compared to asymptomatic sarcoidosis (1-2 times). The causal relationship between sarcoidosis and bronchogenic carcinoma is unclear. It has been postulated that fibrous tissue and cell mediated immune abnormalities in sarcoidosis can predispose to lung cancer. Oncocentric theory postulates granulomatous inflammation as an immunological reaction to tumor antigen. Our patient's diagnosis of lung cancer was delayed as the initial needle biopsy only detected coexisting granulomas and later found to have adenocarcinoma on wedge biopsies. We want to report this case to remind the association of granulomatous inflammation and sarcoidosis with bronchogenic carcinoma. Other important learning point is to pursue further diagnostic procedures if initial biopsies show only granulomas especially in case of high pretest probability of lung cancer.