Pulmonary lymphomatoid granulomatosis (PLG) is a rare Epstein-Barr virus (EBV)-driven B-cell lymphoproliferative disorder characterized by angiocentric and angiodestructive infiltrates. The disease predominantly affects middle-aged immunocompromised males, with a median survival of 14 months and mortality rates of 63%-90% at 5 years. Histopathological evaluation remains the cornerstone of diagnosis, historically requiring surgical lung biopsy for adequate tissue acquisition. We present a novel case of an 82-year-old male with a history of COPD and colon cancer who developed rapidly progressive, predominantly right upper lobe pulmonary nodules. The patient's initial presentation with fever and hypotension led to an inpatient workup for sepsis, where his lung nodules were incidentally noted to have grown. Following referral to pulmonology, a robotic navigation bronchoscopy (ion) with a cryoprobe (Erbe) was performed for tissue diagnosis, initially considering metastatic disease. Pathology from the cryoprobe biopsy yielded a consensus diagnosis of Grade 3 PLG after expert review. This case raises awareness of a rare diagnosis in the differential of progressive pulmonary nodules. It also demonstrates an atypical presentation with the patient's advanced age, the aggressive and unusual distribution of the nodules, and the absence of classic extrapulmonary manifestations. Most importantly, it demonstrates that a novel, less invasive, cryoprobe-assisted bronchoscopic biopsy can be sufficient for a definitive diagnosis of this rare disease, a modality not previously reported for PLG diagnosis, potentially precluding the need for more invasive surgical procedures.
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