Introduction: Lymphoid interstitial pneumonia (LIP) is a rare benign lymphoproliferative disorder frequently associated with autoimmune diseases, particularly Sjögren syndrome. Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma represents a low-grade B-cell lymphoma that may arise in the context of chronic immune stimulation. The differential diagnosis and possible coexistence of LIP and MALT lymphoma in patients with autoimmune disease can be demanding, raising diagnostic challenges.

Clinical Case Description: A 76-year-old male patient with multiple sclerosis was hospitalized with hypoxemic respiratory failure due to viral infection. During workup, a chest CT revealed bilateral cystic changes, alongside a 30×23 mm ground-glass nodule in the left upper lobe. PET-CT scan showed moderate FDG uptake. The radiologic pattern was discussed in a multidisciplinary setting, raising a provisional diagnosis of LIP.

The patient underwent transthoracic lung biopsy, which was later deemed inconclusive, and was discharged. A second biopsy demonstrated a dense lymphoplasmacytic infiltrate with B-cell phenotype, consistent with MALT lymphoma.

Further evaluation revealed complaints of xerostomia and a positive anti-SSA/Ro60 antibodies, consistent with Sjögren syndrome. Viral serologies were negative. Pulmonary function tests were inconclusive due to poor collaboration. 

Conclusions: This case highlights the diagnostic challenges regarding cystic lung diseases in the setting of autoimmune disorders and lymphoproliferative conditions. In patients with Sjögren syndrome, cystic lung changes may reflect different, potentially overlapping entities, including LIP and MALT lymphoma, which may be difficult to distinguish both radiologically and histologically.

Chronic antigenic stimulation is thought to underlie this spectrum, ranging from polyclonal lymphoid proliferation, as seen in LIP, to monoclonal expansion in lymphoma. Although progression from LIP to lymphoma is rare, it has been described and supports the concept of a continuum of lymphoproliferative disorders.

Recognition of this overlap is essential, as it has important implications for diagnosis, surveillance, and management, requiring careful integration of clinical, radiological, and histopathological data within a multidisciplinary framework.