An 18-year-old man was hospitalized with intense thirst, polyuria, polydypsia, and weight loss. The oral mucosa appeared slightly dry, and mild hepatosplenomegaly was present. The physical examination was otherwise unremarkable. Diabetes mellitus and insipidus were ruled out by laboratory tests and imaging of the head. Fever and pancytopenia, in the absence of signs of disease other than xerostomia, prompted us to take a biopsy specimen from the bone marrow. Lymphoblastic lymphoma was diagnosed, polychemotherapy produced complete remission, and xerostomia disappeared. Two relapses were heralded by xerostomia that disappeared after remission was obtained through salvage protocols. The patient died of aspergillotic pneumonia during drug-induced pancytopenia. His salivary glands were clinically and histologically (Figure 1, panel A) normal, and no antinuclear antibodies were present in his serum, thus excluding the Sjogren syndrome [1].

View larger version (123K): [in this window] [in a new window]   Figure 1. A. Normal histologic appearance of the patient's salivary gland (hematoxylin and eosin stain; original magnification, x40). B. The patient's serum immunostains monkey salivary ducts on indirect mmunofluorescence (original magnification, x40). (Courtesy of Drs. E. Bosi and A. M. Girardi.) C. The patient's IgG levels are detectable in the ductal and acinar cells of his parotid gland on direct immunocytochemistry (original magnification, x40). D. The patient's IgG reacts preferentially with the cytoplasm of the acinar cells of his parotid gland, leaving nuclei unstained (direct immunocytochemistry; original magnification, x80).

To investigate the nonfortuitous relation between xerostomia and lymphoma, we looked for autoantibodies to the salivary glands in the patient's serum. Circulating autoantibodies against the ductal cells of monkey salivary glands were demonstrated by indirect immunofluorescence at each relapse and during the second remission (Figure 1, panel B). The presence of autoantibodies was shown by direct immunocytochemistry in the patient's parotid gland (Figure 1, panels C and D).

Autoantibodies directed against cellular antigens are present in patients with a malignant condition [2]. Although rarely pathogenic [3], autoantibodies can be considered markers of an impending tumor because they can precede the appearance of clinically detectable cancer [4, 5]. To our knowledge, paraneoplastic autoimmune xerostomia has never been reported. Although the cellular target of these autoantibodies is unknown, we hypothesize that they might play a pathogenic role inhibiting salivary secretion.

We suggest that the sudden appearance of xerostomia together with autoantibodies to the salivary glands-after exclusion of the Sjogren syndrome, direct infiltration of the salivary glands by neoplasia, and primary disorders of water balance-should prompt a careful search for occult cancer.