Abstract Introduction Malignant neoplasms of the lung include non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), which rarely coexist within the same patient. This rarity is further compounded by the simultaneous presence of sarcoidosis or sarcoid-like granulomatous inflammation. We present a 65-year-old male with COPD and prior renal cell carcinoma found to have both SCC and SCLC in mediastinal lymph nodes in addition to non-caseating granulomas and hypercalcemia. Case Description A 65-year-old male with a history of COPD, tobacco use disorder, and renal cell carcinoma status post right nephrectomy presented with hemoptysis. Initial laboratory evaluation revealed marked hypercalcemia (total calcium 19 mg/dL, ionized calcium 2.33 mmol/L). Chest CT demonstrated emphysema, a spiculated 7 mm nodule in the left upper lobe, a 6 mm calcified nodule in the left lower lobe, diffuse bilateral tree-in-bud nodularity, bulky bilateral hilar and mediastinal lymphadenopathy with calcifications, and enlarged axillary lymph nodes. Further workup for hypercalcemia revealed ACE 11 U/L, 1,25-dihydroxyvitamin D 39 pg/mL, and PTHrP 56 pmol/L. Bronchoscopy with endobronchial ultrasound-guided biopsy (EBUS) revealed rare squamous epithelium in lymph node 11L, non-caseating granulomas in node 7, findings suspicious for small cell carcinoma in node 4R, and squamous cell carcinoma in node 11R. These findings raised concern for dual malignancies with possible concurrent sarcoidosis. Hematology/Oncology was consulted for further evaluation. Immunohistochemical and molecular testing demonstrated p40 and p63 positivity, Ki-67 proliferation index of 90%, and PD-L1 expression of 75%. Given the overlapping diagnoses of small cell and squamous cell carcinoma and the absence of a clear primary lesion, the patient was diagnosed with stage IV lung cancer of mixed histology. He was initiated on combination chemoimmunotherapy with carboplatin, paclitaxel, and pembrolizumab, along with palliative denosumab for hypercalcemia management. Discussion The coexistence of small cell and squamous cell carcinoma diagnosed concurrently in different lymph nodes is exceedingly rare, with combined NSCLC/SCLC phenotypes accounting for only about 4% of all lung cancers. The additional findings of non-caseating granulomas and recurrent episodes of hypercalcemia further complicated the clinical picture, suggesting not true sarcoidosis, but rather an evolving paraneoplastic process. This distinction was crucial in diagnosis as management and treatment are specific to the underlying cause. This case adds to the limited reports describing synchronous small cell and squamous cell carcinoma associated with sarcoid-like granulomatous reactions and the importance of prompt biopsy and treatment. This abstract is funded by: None
McCauley et al. (Fri,) studied this question.