We reported a case of foreign body-type giant cell reaction with intense [18F]FDG uptake following chemotherapy in a patient with DLBCL, without the presence of a foreign body. The finding is thought to be due to rapid, extensive tumor necrosis in response to chemotherapy, with persistent accumulation and activation of macrophages to clean up the dying cells, as evidenced by the presence of extensive vascularization on histological examination. The “foreign body” in our case was the actual tumor dying rapidly. Typically, giant cells are formed by fusion of various cells such as macrophages, epithelioid cells, histiocytes and monocytes to become multinucleate cells that surround the foreign material or inflamed tissue (Brodbeck and Anderson 2009).
Although foreign body-type giant cell reaction with biological and immunological response to foreign bodies has been more frequently reported (Brodbeck and Anderson 2009; Sheikh et al. 2015), it has also been reported in the setting of tumor necrosis, probably mediated by cytokines such as tumor necrosis factor (Brooks et al. 2019). In a patient with renal cell carcinoma following cryoablation, Kahn et al. (2019) described a surgically resected retroperitoneal perinephric mass thought to be recurrent renal cell carcinoma that was pathologically confirmed as tumefactive fat necrosis with multinucleate giant cell reaction. In a historical study assessing changes of metastatic lymph nodes of the squamous cell type after radiation (McGregor 1934), Dr. McGregor stated “Giant cells of the foreign body type were always found in radiated and non-radiated nodes wherever necrotic cancer came directly in contact with lymph node tissues” and “The presence of these giant cells must be regarded as a favorable sign.” In a study of 5 patients with lymphoma, development of post-chemotherapy histiocyte-rich pseudotumor was reported (Goebel et al. 2021). It was thought that in a setting of massive tumor cell apoptosis following chemotherapy, the normal clearance mechanisms are overwhelmed and proinflammatory intracellular contents, known as damage-associated molecular patterns, are released from the cell, inducing histiocyte recruitment.
The inflammatory process with foreign body-type giant cell reaction is known to be associated with increased [18F]FDG uptake on [18F]FDG PET scan (Erdoğan et al. 2013; Dong et al. 2016; Miyake et al. 2010; Rahier and Deprez 2018), with reported SUVmax ranged at 9.1–28.0 (average: 17.6). In the present case, the markedly intense uptake (SUVmax of 68) is rarely observed, likely indicative of rapid tumor response to chemotherapy with extensive tumor necrosis and active inflammatory process.
In conclusion, highly [18F]FDG avid lesion with foreign body-type giant cell reaction could occur without the presence of a foreign body and may be indicative of rapidly dying tumor cells in initial response to chemotherapy. We concluded that the intensity of [18F]FDG uptake in the suspected lesion in diffuse large B cell lymphoma following chemotherapy may be nonspecific and should not be used as the diagnostic criterion for malignancy.