Granulomatosis and Cancer

Sarcoidosis is a granulomatous disease of unknown cause that can virtually affect any organ system. The commonly affected organ areas are thoracic lymph nodes and lungs (90 %). The granulomas appears to be due to an aberant immune response to a persistent antigen in a susceptible host; the antigen, however, is yet to be identified(Shigemitsu, 2008). The diagnosis typically rests on the demonstration of characteristic granulomas in biopsy specimens of one or more organs and exclusion of other causes of chronic granulomatous inflammation(Boffetta et al., 2009; Pavic et al., 2008b). Sarcoidosis affects more frequently young adults. Genetic studies have shown that some major histocompatibility complex alleles and tumor necrosis factor (TNF) polymorphisms are associated with an increased risk of sarcoidosis. The disease is usually characterized by an increased macrophage and CD4 Tcell activation, whereas sarcoidosis patients also show suppressed response to antigen challenges. The coexistent of hyperand hypoactivity indicates a state of anergy in the immune system(Ji et al., 2009). Relationships betwen granulomatosis and cancers have been suspected for a long time(Askling et al., 1999; Brincker and Wilbek, 1974; Pavic and Rousset, 2008; Romer et al., 1998). Nevertheless, few evidence has been reported until recently. Aside from granulomatosis due to infectious disease (eg: opportunist infections), granulomas can be observed in cancer patients, mainly in two situations. Patients may rarely present with typical sarcoidosis occuring before, during or after the diagnosis of cancer. Secondly granulomas may be found as a sarcoid reaction in the vicinity of the tumour itself ore more frequently in regional lymph nodes(Pavic et al., 2008a). Sarcoidosis has although been reported to occur with some chemotherapeutic agents or immunotherapy such as interferon. The presence of granulomas within the tumor tissue or in regional ganglions is a frequent situation and corresponds to a defense reaction against the tumor-associated antigen (sarcoid like reaction)(Kennedy et al., 2008; Steinfort and Irving, 2009). The precise mechanism of the sarcoid-cancer syndrome is not yet clear, though there are several descriptions in the literature as to the temporal relationship of granulomas developing in cancer and vice versa. The etiology of sarcoidosis and sarcoid reactions in malignancy remains uncertain but some speculations have been made(Trikudanathan et al.): 1/ induction of robust effector T cell response to a tumor antigen or other products of cancer cells either spontaneously or with treatment that result in T helper 1 response along with secretion of TH1 cytokines; 2/ increased vulnerability to a potential infective agent due to immune system imbalance that occurs with cancer; 3/ radiation therapy and antineoplastic agents might enhance granulomatous reactions in tumors; 4/granulomatous reaction could