The most likely diagnosis is IgG4-related disease, a recently described condition characterized by lymphoplasmacytic infiltration and enlargement of various structures, including the pancreas, lymph nodes, salivary glands, periaortic region leading to retroperitoneal fibrosis, kidneys, and skin. Most patients are men (60%-80%) over the age of 50 years. Typical presentation is the subacute development of a mass in the affected organ (for example, an orbital pseudotumor) or diffuse organ enlargement. Up to 90% of patients have multiple organ involvement. Lymphadenopathy is common, as is lacrimal and salivary gland involvement. Most patients lack constitutional symptoms at the time of diagnosis and generally feel well. Staining for IgG4-producing plasma cells reveals large numbers in the tissue.

Hodgkin lymphoma usually presents with palpable lymphadenopathy or a mediastinal mass that requires tissue biopsy for diagnosis. Biopsy is likely to show mainly clonal malignant Hodgkin/Reed-Sternberg cells in a background of granulocytes, plasma cells, and lymphocytes. Reed-Sternberg cells appear as large cells with large, pale nuclei containing large purple nucleoli, and their appearance is indicative of Hodgkin disease. The patient's biopsy findings are not consistent with Hodgkin lymphoma.

Sarcoidosis is a multisystem disease characterized by noncaseating granulomas that form in tissues and most commonly affects the lungs. The absence of granulomas on biopsy is helpful to distinguish IgG4-related disease from sarcoidosis.

Sjögren syndrome can present with enlargement of the salivary glands. However, it is associated with focal, centrilobular collections of lymphocytes on biopsy without the histology characteristic for IgG4-related disease present in this patient. Patients with Sjögren syndrome also usually have positive anti-Ro/SSA and anti-La/SSB antibodies, which are not present in this patient.