The use of 18F-FDG PET has evolved in the last few decades and is now considered one of the mainstays of diagnosis and staging as well as of monitoring the effects of treatment in the field of oncology. However, the uptake of FDG is not specific : uptake is seen not only in normal organs but also in other non-neoplastic etiologies such as inflammatory, reactive, or infectious causes. RDD, as a benign lymphoproliferative disorder, is generally believed to be FDG-avid. Clinically, RDD is commonly associated with lymphadenopathy of the cervical region, but involvement of extranodal organs such as the skin and paranasal sinuses is not rare . Consequently, the isolated or widespread FDG-avid lesions of RDD can mimic malignancies and thus lead to a false image interpretation. Therefore, RDD that exhibits massive lymphadenopathy or extranodal manifestations or both should be considered in the differential diagnosis of a malignant process, such as lymphoma or metastatic tumors.
An elevated serum titer of IgG4 is a surrogate marker for the recently characterized IgG4-RSD in multiple extra-pancreatic sites with or without an accompanying pancreatic lesion . Pathologically, IgG4-RSD is an inflammatory or fibrosing disease process (or both) characterized by the presence of a prominent number of IgG4+ plasma cells within the affected tissues . Although there is no consensus about the definite cutoff limit for the number of IgG4+ plasma cells and the ratio of IgG4+ to IgG+ cells as the diagnostic criteria for IgG4-RSD, immunostaining shows an absolute number of IgG4+ cells of greater than 50 per high-powered field, and an IgG4+/IgG+ cell ratio of greater than 40% is well accepted by investigators .
Generally, both RDD and IgG4-RSD have been proven to be FDG-avid [13, 14]. Although the mechanism of RDD and IgG4-RSD with increased FDG uptake is not certain, it has been well documented that variable expression of the glucose transporters may depend on expression of varying stress-related proteins or signaling molecules induced by activated macrophages (histiocytes) and lymphocytes . In previous 18F-FDG PET reports, RDD revealed as hypermetabolic lesions was found within the thyroid, skin, and bones, where FDG-PET was used for staging the supposed malignancy and surveying the extent of RDD [4, 16]. For IgG4-RSD, FDG-PET was suggested as an effective modality to provide extra-pancreatic biopsy sites, monitor therapy, and demonstrate relapse . To the best of our knowledge, no report of FDG PET/CT findings of RDD with IgG4+ plasma cell infiltration has been published, although a series of pathological research has focused on this phenomenon. In our case, the hypermetabolic soft-tissue nodule in the right breast accompanied by multiple active pulmonary nodules mimicked breast malignancy with lung metastasis. Even in a review of the PET/CT images, it seemed unfeasible to discriminate the nature of FDG-avid breast RDD from carcinoma simply by the distribution pattern or intensity of the FDG accumulation. In addition, the pancreas, hepatobiliary system, and glandular organs, which are the most common sites involved in IgG4-RSD, showed no abnormal FDG accumulation in our patient. In this case, the value of 18F-FDG PET/CT is mainly in localizing the proper target sites for tissue biopsy and thereby confirming the diagnosis and helping to adjust the clinical treatment strategy.
It is interesting to find amyloid deposition rather than abundant histiocytes or IgG4+ plasma cell accumulation within pulmonary nodules. In addition, amyloidosis was still observed in the connective tissues surrounding the cervical LNs. For PET/CT images, the slight FDG uptake at the edge of the solid pulmonary nodule was different from the typical radioactivity distribution pattern of hematogenous metastatic lesions, which corresponded well to the pathological findings of diffuse amyloid deposition accompanied by few histiocytic infiltrations at the boundary of the samples. Pulmonary amyloidosis was previously reported as multiple nodules with slight FDG uptake and which were raised suspicion of metastasis from a hidden malignancy . Therefore, it is suggested that, in the event of multiple irregular variable-sized nodules with the special FDG distribution pattern in both lungs, certain kinds of non-tumor diseases should be taken into diagnostic consideration. Though rare, amyloidosis ought to be kept in mind as a differential diagnosis of metastatic lesions. In fact, amyloidosis is caused by the extracellular deposition of pathological, insoluble, fibrillar proteins in organs and tissues. Secondary amyloidosis is caused by the deposition of amyloid originating from serum amyloid A, which is an acute-phase protein produced in response to inflammation and occurs most commonly among patients with chronic inflammatory diseases such as rheumatoid arthritis, juvenile rheumatoid arthritis, and inflammatory bowel disease . The reason for the amyloid deposition in this case is not clear, but a plausible postulation is that it was associated with the chronic inflammatory stimulation of the mammary lesion and/or autoimmune abnormalities represented by raised serum polyclonal immunoglobulins and low titers of autoantibodies. Further studies may be needed to explore the underpinning relationship between serum amyloid A and autoimmune disease, RDD and IgG4-RSD.